Tomas Kirchhausen

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Research Overview

Our research has helped defined the structure, interactions, and assembly-disassembly mechanisms of clathrin and many of its associated proteins, through studies extending over three decades. Our work has been characterized by use of emerging technologies -- from the early days of molecular cloning to contemporary high-resolution structural visualization and live-cell imaging. We have used the tools of x-ray crystallography, cryo electron microscopy, and single-molecule biophysics to create a "molecular movie" of clathrin-mediated endocytosis, and in this way related these molecular events to functional properties of the surfaces of living cells. We also use frontier optical-imaging modalities to examine other cellular membrane remodeling processes exemplified by the formation of intraluminal vesicles and nuclear pores.

Our molecular snapshots led to the first structure determination at atomic resolution of large portions of clathrin and AP-1, key components of the clathrin coat. We used cryo electron microscopy to obtain the first visualization of a complete clathrin coat at 8 Å resolution and thereby unveiled the basic structure of the triskelion leg and established the way triskelions pack when they form the clathrin coat. We then establish how auxilin and Hsc70 mediate the ATP-dependent uncoating step by visualizing a complete clathrin coat bound to auxilin and Hsc70 at 12-15 Å resolution. We continued with this structural approach and determined the mode of interaction of ß-arrestins and adaptors with clathrin and on the linkage between the clathrin machinery and the non-canonical Wnt-signaling pathway.

Direct observation of molecular events in vivo is the ultimate goal of contemporary microscopy. Two recently developed forms of fluorescence microscopy available in our laboratory -- Lattice Light Sheet Microscopy (LLSM) and Lattice Light Sheet Microscopy optimized with Adaptive Optics (AO-LLSM) -- are poised to bridge the gap between molecules and cells, either as independent entities in culture, as components of organoids, or as components of living tissues. The richness and magnitude of the data over periods ranging from seconds to hours, create new challenges for obtaining quantitative representations of the observed dynamics and for deriving accurate and comprehensive models for the underlying developmental mechanisms.

With these type of dynamic studies we expect to integrate molecular snapshots obtained at high resolution with live-cell processes, in an effort to generate other ‘molecular movies' allowing us to obtain new frameworks for analyzing some of the molecular contacts and switches that participate in the regulation, availability, and intracellular traffic of the many molecules involved in signal transduction, immune responsiveness, lipid homeostasis, cell-cell recognition and organelle biogenesis. Such biological phenomena have importance for our understanding of many diseases including cancer, viral infection and pathogen invasion, Alzheimer's, as well as other neurological diseases.

Research Background

Dr. Kirchhausen is a Professor of Cell Biology and of Pediatrics at Harvard Medical School and the Springer Family Chair of Pediatrics and a Senior investigator at Boston Children’s Hospital. He received his undergraduate degree in Biology from the Universidad Peruana Cayetano Heredia and earned his Ph.D. in Biophysics from the Instituto Venezolano de Investigaciones Cientificas.

The animation by Janet Iwasa and Tom Kirchhausen showing the process of clathrin-mediated endocytosis won the 1st Place Video at the Celldance 2008 contest of the American Society of Cell Biology and was one of the scientific animations highlighted by Erik Olsen in his article "The Animators of Life" published in The New York Times, November 15, 2010.

The YouTube 3D movie by Tsung-Li Liu,, Srigokul (Gokul) Upadhyayula, Eric Betzig, Tom Kirchhausen and colleagues acquired using AO-LLSM and showing the migration of immune cells in the zebrafish inner ear has been downloaded more than 700,000 times.

Publications

Neuronal constitutive endolysosomal perforations enable a-synuclein aggregation by internalized PFFs. J Cell Biol. 2025 Feb 03; 224(2). View Abstract
CryoSamba: Self-supervised deep volumetric denoising for cryo-electron tomography data. J Struct Biol. 2024 Dec 20; 217(1):108163. View Abstract
Molecularly Distinct Clathrin-Coated Pits Differentially Impact EGFR Fate and Signaling. Cell Rep. 2024 Nov 26; 43(11):114970. View Abstract
CryoSamba: self-supervised deep volumetric denoising for cryo-electron tomography data. bioRxiv. 2024 Aug 03. View Abstract
Probing and imaging phospholipid dynamics in live cells. Life Metab. 2024 Aug; 3(4):loae014. View Abstract
Temporal dynamics and stoichiometry in human Notch signaling from Notch synaptic complex formation to nuclear entry of the Notch intracellular domain. Dev Cell. 2024 Jun 03; 59(11):1425-1438.e8. View Abstract
Deep learning assisted single particle tracking for automated correlation between diffusion and function. Res Sq. 2024 Feb 02. View Abstract
Constitutive Endolysosomal Perforation in Neurons allows Induction of a-Synuclein Aggregation by Internalized Pre-Formed Fibrils. bioRxiv. 2024 Jan 01. View Abstract
Deep learning assisted single particle tracking for automated correlation between diffusion and function. bioRxiv. 2023 Nov 17. View Abstract
Temporal Dynamics and Stoichiometry in Notch Signaling - from Notch Synaptic Complex Formation to NICD Nuclear Entry. bioRxiv. 2023 Sep 28. View Abstract
A spatiotemporal Notch interaction map from plasma membrane to nucleus. Sci Signal. 2023 08; 16(796):eadg6474. View Abstract
A Serotonergic Axon-Cilium Synapse Drives Nuclear Signaling to Maintain Chromatin Accessibility. Microsc Microanal. 2023 Jul 22; 29(29 Suppl 1):1091. View Abstract
Complete Protection from SARS-CoV-2 Lung Infection in Mice Through Combined Intranasal Delivery of PIKfyve Kinase and TMPRSS2 Protease Inhibitors. bioRxiv. 2023 Jul 20. View Abstract
Structure-based design of a SARS-CoV-2 Omicron-specific inhibitor. Proc Natl Acad Sci U S A. 2023 03 28; 120(13):e2300360120. View Abstract
Deep neural network automated segmentation of cellular structures in volume electron microscopy. J Cell Biol. 2023 02 06; 222(2). View Abstract
The beauty of simplicity in membrane biology. Nat Cell Biol. 2022 Dec; 24(12):1682-1685. View Abstract
Nanomolar inhibition of SARS-CoV-2 infection by an unmodified peptide targeting the prehairpin intermediate of the spike protein. Proc Natl Acad Sci U S A. 2022 10 04; 119(40):e2210990119. View Abstract
SARS-CoV-2 requires acidic pH to infect cells. Proc Natl Acad Sci U S A. 2022 09 20; 119(38):e2209514119. View Abstract
A serotonergic axon-cilium synapse drives nuclear signaling to alter chromatin accessibility. Cell. 2022 09 01; 185(18):3390-3407.e18. View Abstract
An antibody from single human VH-rearranging mouse neutralizes all SARS-CoV-2 variants through BA.5 by inhibiting membrane fusion. Sci Immunol. 2022 10 28; 7(76):eadd5446. View Abstract
Nanomolar inhibition of SARS-CoV-2 infection by an unmodified peptide targeting the pre-hairpin intermediate of the spike protein. bioRxiv. 2022 Aug 11. View Abstract
SARS-CoV-2 requires acidic pH to infect cells. bioRxiv. 2022 Jun 14. View Abstract
CD164 is a host factor for lymphocytic choriomeningitis virus entry. Proc Natl Acad Sci U S A. 2022 03 08; 119(10):e2119676119. View Abstract
Synergistic Block of SARS-CoV-2 Infection by Combined Drug Inhibition of the Host Entry Factors PIKfyve Kinase and TMPRSS2 Protease. J Virol. 2021 10 13; 95(21):e0097521. View Abstract
Synergistic block of SARS-CoV-2 infection by combined drug inhibition of the host entry factors PIKfyve kinase and TMPRSS2 protease. bioRxiv. 2021 Aug 12. View Abstract
Inherited nuclear pore substructures template post-mitotic pore assembly. Dev Cell. 2021 06 21; 56(12):1786-1803.e9. View Abstract
PKC-phosphorylation of Liprin-a3 triggers phase separation and controls presynaptic active zone structure. Nat Commun. 2021 05 24; 12(1):3057. View Abstract
Activating Sphingosine-1-phospahte signaling in endothelial cells increases myosin light chain phosphorylation to decrease endothelial permeability thereby inhibiting cancer metastasis. Cancer Lett. 2021 05 28; 506:107-119. View Abstract
Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion. Proc Natl Acad Sci U S A. 2020 12 15; 117(50):32105-32113. View Abstract
Design and Validation of a Human Brain Endothelial Microvessel-on-a-Chip Open Microfluidic Model Enabling Advanced Optical Imaging. Front Bioeng Biotechnol. 2020; 8:573775. View Abstract
Tracking Calcium Dynamics and Immune Surveillance at the Choroid Plexus Blood-Cerebrospinal Fluid Interface. Neuron. 2020 11 25; 108(4):623-639.e10. View Abstract
HDAC6 mediates an aggresome-like mechanism for NLRP3 and pyrin inflammasome activation. Science. 2020 09 18; 369(6510). View Abstract
Inhibition of PIKfyve kinase prevents infection by Zaire ebolavirus and SARS-CoV-2. Proc Natl Acad Sci U S A. 2020 08 25; 117(34):20803-20813. View Abstract
Oligomerization of the Vesicular Stomatitis Virus Phosphoprotein Is Dispensable for mRNA Synthesis but Facilitates RNA Replication. J Virol. 2020 06 16; 94(13). View Abstract
Inhibition of PIKfyve kinase prevents infection by Zaire ebolavirus and SARS-CoV-2. bioRxiv. 2020 Jun 15. View Abstract
Dynamics of Auxilin 1 and GAK in clathrin-mediated traffic. J Cell Biol. 2020 03 02; 219(3). View Abstract
Correlative three-dimensional super-resolution and block-face electron microscopy of whole vitreously frozen cells. Science. 2020 01 17; 367(6475). View Abstract
Molecularly Distinct Clathrin-Coated Pits Differentially Impact EGFR Fate and Signaling. Cell Rep. 2019 06 04; 27(10):3049-3061.e6. View Abstract
F-BAR domain only protein 1 (FCHO1) deficiency is a novel cause of combined immune deficiency in human subjects. J Allergy Clin Immunol. 2019 06; 143(6):2317-2321.e12. View Abstract
Cortical column and whole-brain imaging with molecular contrast and nanoscale resolution. Science. 2019 01 18; 363(6424). View Abstract
The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles. Cell Rep. 2018 07 24; 24(4):973-986.e8. View Abstract
Lamellar projections in the endolymphatic sac act as a relief valve to regulate inner ear pressure. Elife. 2018 06 19; 7. View Abstract
Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms. Science. 2018 04 20; 360(6386). View Abstract
Reconstitution of Clathrin Coat Disassembly for Fluorescence Microscopy and Single-Molecule Analysis. Methods Mol Biol. 2018; 1847:121-146. View Abstract
Dynamics of phosphoinositide conversion in clathrin-mediated endocytic traffic. Nature. 2017 12 21; 552(7685):410-414. View Abstract
NRP2 and CD63 Are Host Factors for Lujo Virus Cell Entry. Cell Host Microbe. 2017 Nov 08; 22(5):688-696.e5. View Abstract
Recruitment dynamics of ESCRT-III and Vps4 to endosomes and implications for reverse membrane budding. Elife. 2017 10 11; 6. View Abstract
Ectopic expression of RAD52 and dn53BP1 improves homology-directed repair during CRISPR-Cas9 genome editing. Nat Biomed Eng. 2017 11; 1(11):878-888. View Abstract
Miro1-mediated mitochondrial positioning shapes intracellular energy gradients required for cell migration. Mol Biol Cell. 2017 Aug 01; 28(16):2159-2169. View Abstract
Inhibition of JCPyV infection mediated by targeted viral genome editing using CRISPR/Cas9. Sci Rep. 2016 Nov 14; 6:36921. View Abstract
Scramblase TMEM16F terminates T cell receptor signaling to restrict T cell exhaustion. J Exp Med. 2016 11 14; 213(12):2759-2772. View Abstract
Membrane fission by dynamin: what we know and what we need to know. EMBO J. 2016 11 02; 35(21):2270-2284. View Abstract
Seipin is required for converting nascent to mature lipid droplets. Elife. 2016 Aug 26; 5. View Abstract
Membrane dynamics of dividing cells imaged by lattice light-sheet microscopy. Mol Biol Cell. 2016 11 07; 27(22):3418-3435. View Abstract
Identification and Characterization of a Novel Broad-Spectrum Virus Entry Inhibitor. J Virol. 2016 May; 90(9):4494-4510. View Abstract
Data publication with the structural biology data grid supports live analysis. Nat Commun. 2016 Mar 07; 7:10882. View Abstract
Endocytosis of Ligand-Activated Sphingosine 1-Phosphate Receptor 1 Mediated by the Clathrin-Pathway. Traffic. 2016 Jan; 17(1):40-52. View Abstract
Superinfection exclusion is absent during acute Junin virus infection of Vero and A549 cells. Sci Rep. 2015 Nov 09; 5:15990. View Abstract
ADVANCED IMAGING. Extended-resolution structured illumination imaging of endocytic and cytoskeletal dynamics. Science. 2015 Aug 28; 349(6251):aab3500. View Abstract
Visualizing lipid-formulated siRNA release from endosomes and target gene knockdown. Nat Biotechnol. 2015 Aug; 33(8):870-6. View Abstract
Cytotoxic Cells Kill Intracellular Bacteria through Granulysin-Mediated Delivery of Granzymes. Cell. 2015 May 21; 161(5):1229. View Abstract
Asymmetric formation of coated pits on dorsal and ventral surfaces at the leading edges of motile cells and on protrusions of immobile cells. Mol Biol Cell. 2015 Jun 01; 26(11):2044-53. View Abstract
Role of the clathrin adaptor PICALM in normal hematopoiesis and polycythemia vera pathophysiology. Haematologica. 2015 Apr; 100(4):439-51. View Abstract
In vivo analysis of formation and endocytosis of the Wnt/ß-Catenin signaling complex in zebrafish embryos. J Cell Sci. 2014 Dec 15; 127(24):5331. View Abstract
Dynamin recruitment and membrane scission at the neck of a clathrin-coated pit. Mol Biol Cell. 2014 Nov 05; 25(22):3595-609. View Abstract
Structural correlates of rotavirus cell entry. PLoS Pathog. 2014 Sep; 10(9):e1004355. View Abstract
In vivo analysis of formation and endocytosis of the Wnt/ß-catenin signaling complex in zebrafish embryos. J Cell Sci. 2014 Sep 15; 127(Pt 18):3970-82. View Abstract
Cytotoxic cells kill intracellular bacteria through granulysin-mediated delivery of granzymes. Cell. 2014 Jun 05; 157(6):1309-1323. View Abstract
Key interactions for clathrin coat stability. Structure. 2014 Jun 10; 22(6):819-29. View Abstract
Molecular structure, function, and dynamics of clathrin-mediated membrane traffic. Cold Spring Harb Perspect Biol. 2014 May 01; 6(5):a016725. View Abstract
The timing of pre-mRNA splicing visualized in real-time. Nucleus. 2014 Jan-Feb; 5(1):11-4. View Abstract
Live-cell visualization of pre-mRNA splicing with single-molecule sensitivity. Cell Rep. 2013 Sep 26; 4(6):1144-55. View Abstract
Uptake of rabies virus into epithelial cells by clathrin-mediated endocytosis depends upon actin. J Virol. 2013 Nov; 87(21):11637-47. View Abstract
Clathrin-mediated endocytosis persists during unperturbed mitosis. Cell Rep. 2013 Aug 29; 4(4):659-68. View Abstract
Endocytosis and recycling of immune complexes by follicular dendritic cells enhances B cell antigen binding and activation. Immunity. 2013 Jun 27; 38(6):1164-75. View Abstract
Release of cellular tension signals self-restorative ventral lamellipodia to heal barrier micro-wounds. J Cell Biol. 2013 Apr 29; 201(3):449-65. View Abstract
Similar uptake but different trafficking and escape routes of reovirus virions and infectious subvirion particles imaged in polarized Madin-Darby canine kidney cells. Mol Biol Cell. 2013 Apr; 24(8):1196-207. View Abstract
The small molecule dispergo tubulates the endoplasmic reticulum and inhibits export. Mol Biol Cell. 2013 Apr; 24(7):1020-9. View Abstract
Dynamics of intracellular clathrin/AP1- and clathrin/AP3-containing carriers. Cell Rep. 2012 Nov 29; 2(5):1111-9. View Abstract
Bending membranes. Nat Cell Biol. 2012 Sep; 14(9):906-8. View Abstract
The first five seconds in the life of a clathrin-coated pit. Cell. 2012 Aug 03; 150(3):495-507. View Abstract
Small molecule-mediated TGF-ß type II receptor degradation promotes cardiomyogenesis in embryonic stem cells. Cell Stem Cell. 2012 Aug 03; 11(2):242-52. View Abstract
Regulation of ligand-independent Notch signal through intracellular trafficking. Commun Integr Biol. 2012 Jul 01; 5(4):374-6. View Abstract
Limited transferrin receptor clustering allows rapid diffusion of canine parvovirus into clathrin endocytic structures. J Virol. 2012 May; 86(9):5330-40. View Abstract
Host cell nucleolin is required to maintain the architecture of human cytomegalovirus replication compartments. mBio. 2012; 3(1). View Abstract
Visualizing the high curvature regions of post-mitotic nascent nuclear envelope membrane. Commun Integr Biol. 2012 Jan 01; 5(1):16-8. View Abstract
Live-cell imaging of clathrin coats. Methods Enzymol. 2012; 505:59-80. View Abstract
Synergy between the ESCRT-III complex and Deltex defines a ligand-independent Notch signal. J Cell Biol. 2011 Dec 12; 195(6):1005-15. View Abstract
Human cytomegalovirus UL44 concentrates at the periphery of replication compartments, the site of viral DNA synthesis. J Virol. 2012 Feb; 86(4):2089-95. View Abstract
Actin dynamics counteract membrane tension during clathrin-mediated endocytosis. Nat Cell Biol. 2011 Aug 14; 13(9):1124-31. View Abstract
Formation of the postmitotic nuclear envelope from extended ER cisternae precedes nuclear pore assembly. J Cell Biol. 2011 Aug 08; 194(3):425-40. View Abstract
Recruitment of cellular clathrin to viral factories and disruption of clathrin-dependent trafficking. Traffic. 2011 Sep; 12(9):1179-95. View Abstract
Perforin pores in the endosomal membrane trigger the release of endocytosed granzyme B into the cytosol of target cells. Nat Immunol. 2011 Jun 19; 12(8):770-7. View Abstract
Redistribution of caveolae during mitosis. J Cell Sci. 2011 Jun 15; 124(Pt 12):1965-72. View Abstract
ARFGAP1 promotes AP-2-dependent endocytosis. Nat Cell Biol. 2011 May; 13(5):559-67. View Abstract
Single-molecule analysis of a molecular disassemblase reveals the mechanism of Hsc70-driven clathrin uncoating. Nat Struct Mol Biol. 2011 Mar; 18(3):295-301. View Abstract
Structural analysis of the interaction between Dishevelled2 and clathrin AP-2 adaptor, a critical step in noncanonical Wnt signaling. Structure. 2010 Oct 13; 18(10):1311-20. View Abstract
The length of vesicular stomatitis virus particles dictates a need for actin assembly during clathrin-dependent endocytosis. PLoS Pathog. 2010 Sep 30; 6(9):e1001127. View Abstract
Structure of the PTEN-like region of auxilin, a detector of clathrin-coated vesicle budding. Structure. 2010 Sep 08; 18(9):1191-8. View Abstract
Structural biology: Conservation in vesicle coats. Nature. 2010 Aug 26; 466(7310):1048-9. View Abstract
Shiga toxin increases formation of clathrin-coated pits through Syk kinase. PLoS One. 2010 Jul 27; 5(7):e10944. View Abstract
Roles of AP-2 in clathrin-mediated endocytosis. PLoS One. 2010 May 12; 5(5):e10597. View Abstract
Protein complexes containing CYFIP/Sra/PIR121 coordinate Arf1 and Rac1 signalling during clathrin-AP-1-coated carrier biogenesis at the TGN. Nat Cell Biol. 2010 Apr; 12(4):330-40. View Abstract
Lethal skeletal dysplasia in mice and humans lacking the golgin GMAP-210. N Engl J Med. 2010 Jan 21; 362(3):206-16. View Abstract
Perforin activates clathrin- and dynamin-dependent endocytosis, which is required for plasma membrane repair and delivery of granzyme B for granzyme-mediated apoptosis. Blood. 2010 Feb 25; 115(8):1582-93. View Abstract
Structure of clathrin coat with bound Hsc70 and auxilin: mechanism of Hsc70-facilitated disassembly. EMBO J. 2010 Feb 03; 29(3):655-65. View Abstract
Imaging endocytic clathrin structures in living cells. Trends Cell Biol. 2009 Nov; 19(11):596-605. View Abstract
Distinct dynamics of endocytic clathrin-coated pits and coated plaques. PLoS Biol. 2009 Sep; 7(9):e1000191. View Abstract
Cisternal organization of the endoplasmic reticulum during mitosis. Mol Biol Cell. 2009 Aug; 20(15):3471-80. View Abstract
Vesicular stomatitis virus enters cells through vesicles incompletely coated with clathrin that depend upon actin for internalization. PLoS Pathog. 2009 Apr; 5(4):e1000394. View Abstract
Lymphocyte crawling and transendothelial migration require chemokine triggering of high-affinity LFA-1 integrin. Immunity. 2009 Mar 20; 30(3):384-96. View Abstract
The anaplastic lymphoma kinase controls cell shape and growth of anaplastic large cell lymphoma through Cdc42 activation. Cancer Res. 2008 Nov 01; 68(21):8899-907. View Abstract
Mammalian cells change volume during mitosis. PLoS One. 2008 Jan 23; 3(1):e1477. View Abstract
Use of dynasore, the small molecule inhibitor of dynamin, in the regulation of endocytosis. Methods Enzymol. 2008; 438:77-93. View Abstract
Identification of the molecular target of small molecule inhibitors of HDL receptor SR-BI activity. Biochemistry. 2008 Jan 08; 47(1):460-72. View Abstract
Invasive and adherent bacterial pathogens co-Opt host clathrin for infection. Cell Host Microbe. 2007 Nov 15; 2(5):340-51. View Abstract
Differential evanescence nanometry: live-cell fluorescence measurements with 10-nm axial resolution on the plasma membrane. Biophys J. 2008 Mar 15; 94(6):2333-42. View Abstract
A motif in the clathrin heavy chain required for the Hsc70/auxilin uncoating reaction. Mol Biol Cell. 2008 Jan; 19(1):405-13. View Abstract
Detection of molecular particles in live cells via machine learning. Cytometry A. 2007 Aug; 71(8):563-75. View Abstract
Tracking molecular particles in live cells using fuzzy rule-based system. Cytometry A. 2007 Aug; 71(8):576-84. View Abstract
An ACAP1-containing clathrin coat complex for endocytic recycling. J Cell Biol. 2007 Jul 30; 178(3):453-64. View Abstract
Making COPII coats. Cell. 2007 Jun 29; 129(7):1251-2. View Abstract
PI4P promotes the recruitment of the GGA adaptor proteins to the trans-Golgi network and regulates their recognition of the ubiquitin sorting signal. Mol Biol Cell. 2007 Jul; 18(7):2646-55. View Abstract
Endosomal recycling controls plasma membrane area during mitosis. Proc Natl Acad Sci U S A. 2007 May 08; 104(19):7939-44. View Abstract
Targeting of AMSH to endosomes is required for epidermal growth factor receptor degradation. J Biol Chem. 2007 Mar 30; 282(13):9805-9812. View Abstract
Association of Dishevelled with the clathrin AP-2 adaptor is required for Frizzled endocytosis and planar cell polarity signaling. Dev Cell. 2007 Jan; 12(1):129-41. View Abstract
Large scale synthesis of the Cdc42 inhibitor secramine A and its inhibition of cell spreading. Org Biomol Chem. 2006 Nov 21; 4(22):4149-57. View Abstract
Inhibition of dynamin completely blocks compensatory synaptic vesicle endocytosis. Proc Natl Acad Sci U S A. 2006 Nov 21; 103(47):17955-60. View Abstract
Macropinocytosis: regulated coordination of endocytic and exocytic membrane traffic events. J Cell Sci. 2006 Nov 15; 119(Pt 22):4758-69. View Abstract
Cryo-electron tomography of clathrin-coated vesicles: structural implications for coat assembly. J Mol Biol. 2007 Jan 19; 365(3):892-9. View Abstract
Role of lipids and actin in the formation of clathrin-coated pits. Exp Cell Res. 2006 Dec 10; 312(20):4036-48. View Abstract
Structure determination of clathrin coats to subnanometer resolution by single particle cryo-electron microscopy. J Struct Biol. 2006 Dec; 156(3):453-60. View Abstract
A burst of auxilin recruitment determines the onset of clathrin-coated vesicle uncoating. Proc Natl Acad Sci U S A. 2006 Jul 05; 103(27):10265-10270. View Abstract
Dynasore, a cell-permeable inhibitor of dynamin. Dev Cell. 2006 Jun; 10(6):839-50. View Abstract
Synthesis of a 10,000-membered library of molecules resembling carpanone and discovery of vesicular traffic inhibitors. J Am Chem Soc. 2006 Apr 26; 128(16):5391-403. View Abstract
The Cdc42 inhibitor secramine B prevents cAMP-induced K+ conductance in intestinal epithelial cells. Biochem Pharmacol. 2006 Jun 14; 71(12):1720-6. View Abstract
Secramine inhibits Cdc42-dependent functions in cells and Cdc42 activation in vitro. Nat Chem Biol. 2006 Jan; 2(1):39-46. View Abstract
Perforin triggers a plasma membrane-repair response that facilitates CTL induction of apoptosis. Immunity. 2005 Sep; 23(3):249-62. View Abstract
An emergency response team for membrane repair. Nat Rev Mol Cell Biol. 2005 Jun; 6(6):499-505. View Abstract
The small G-protein Arf6GTP recruits the AP-2 adaptor complex to membranes. J Biol Chem. 2005 Jun 03; 280(22):21661-6. View Abstract
Possible role of deep tubular invaginations of the plasma membrane in MHC-I trafficking. Exp Cell Res. 2005 May 15; 306(1):142-9. View Abstract
Endocytosis is not required for the selective lipid uptake mediated by murine SR-BI. Biochim Biophys Acta. 2005 May 01; 1734(1):44-51. View Abstract
Single-molecule live-cell imaging of clathrin-based endocytosis. Biochem Soc Symp. 2005; (72):71-6. View Abstract
The transcription factor NFAT3 mediates neuronal survival. J Biol Chem. 2005 Jan 28; 280(4):2818-25. View Abstract
Molecular model for a complete clathrin lattice from electron cryomicroscopy. Nature. 2004 Dec 02; 432(7017):573-9. View Abstract
Structure of an auxilin-bound clathrin coat and its implications for the mechanism of uncoating. Nature. 2004 Dec 02; 432(7017):649-53. View Abstract
Crystal structure of the clathrin adaptor protein 1 core. Proc Natl Acad Sci U S A. 2004 Sep 28; 101(39):14108-13. View Abstract
Endocytosis by random initiation and stabilization of clathrin-coated pits. Cell. 2004 Sep 03; 118(5):591-605. View Abstract
The small chemical vacuolin-1 inhibits Ca(2+)-dependent lysosomal exocytosis but not cell resealing. EMBO Rep. 2004 Sep; 5(9):883-8. View Abstract
Effects of dynamin inactivation on pathways of anthrax toxin uptake. Eur J Cell Biol. 2004 Jul; 83(6):281-8. View Abstract
Chemical genetic screening identifies sulfonamides that raise organellar pH and interfere with membrane traffic. Traffic. 2004 Jul; 5(7):478-92. View Abstract
Retrograde transport of cholera toxin from the plasma membrane to the endoplasmic reticulum requires the trans-Golgi network but not the Golgi apparatus in Exo2-treated cells. EMBO Rep. 2004 Jun; 5(6):596-601. View Abstract
Cholera toxin toxicity does not require functional Arf6- and dynamin-dependent endocytic pathways. Mol Biol Cell. 2004 Aug; 15(8):3631-41. View Abstract
Cross-inhibition of SR-BI- and ABCA1-mediated cholesterol transport by the small molecules BLT-4 and glyburide. J Lipid Res. 2004 Jul; 45(7):1256-65. View Abstract
The delta region of outer-capsid protein micro 1 undergoes conformational change and release from reovirus particles during cell entry. J Virol. 2003 Dec; 77(24):13361-75. View Abstract
HIV Nef-mediated major histocompatibility complex class I down-modulation is independent of Arf6 activity. Mol Biol Cell. 2004 Jan; 15(1):323-31. View Abstract
T cells induce extended class II MHC compartments in dendritic cells in a Toll-like receptor-dependent manner. J Immunol. 2003 Oct 15; 171(8):4081-8. View Abstract
Phosphatidylinositol 4 phosphate regulates targeting of clathrin adaptor AP-1 complexes to the Golgi. Cell. 2003 Aug 08; 114(3):299-310. View Abstract
Phenotypic screening of small molecule libraries by high throughput cell imaging. Comb Chem High Throughput Screen. 2003 Jun; 6(4):279-86. View Abstract
Exo1: a new chemical inhibitor of the exocytic pathway. Proc Natl Acad Sci U S A. 2003 May 27; 100(11):6469-74. View Abstract
Constriction and Dnm1p recruitment are distinct processes in mitochondrial fission. Mol Biol Cell. 2003 May; 14(5):1953-63. View Abstract
Discovery of chemical inhibitors of the selective transfer of lipids mediated by the HDL receptor SR-BI. Proc Natl Acad Sci U S A. 2002 Nov 26; 99(24):15422-7. View Abstract
T-cell engagement of dendritic cells rapidly rearranges MHC class II transport. Nature. 2002 Aug 29; 418(6901):983-8. View Abstract
The mu2 subunit of the clathrin adaptor AP-2 binds to FDNPVY and YppØ sorting signals at distinct sites. Traffic. 2002 Aug; 3(8):590-600. View Abstract
L1 endocytosis is controlled by a phosphorylation-dephosphorylation cycle stimulated by outside-in signaling by L1. J Cell Biol. 2002 Jun 24; 157(7):1223-32. View Abstract
Clathrin adaptors really adapt. Cell. 2002 May 17; 109(4):413-6. View Abstract
Single-handed recognition of a sorting traffic motif by the GGA proteins. Nat Struct Biol. 2002 Apr; 9(4):241-4. View Abstract
Structure of the Sec23p/24p and Sec13p/31p complexes of COPII. Proc Natl Acad Sci U S A. 2001 Sep 11; 98(19):10704-9. View Abstract
Use of biomimetic diversity-oriented synthesis to discover galanthamine-like molecules with biological properties beyond those of the natural product. J Am Chem Soc. 2001 Jul 11; 123(27):6740-1. View Abstract
Three ways to make a vesicle. Nat Rev Mol Cell Biol. 2000 Dec; 1(3):187-98. View Abstract
Cdc42 is required for PIP(2)-induced actin polymerization and early development but not for cell viability. Curr Biol. 2000 Jun 29; 10(13):758-65. View Abstract
Multivalent binding of nonnative substrate proteins by the chaperonin GroEL. Cell. 2000 Mar 03; 100(5):561-73. View Abstract
Peptide-in-groove interactions link target proteins to the beta-propeller of clathrin. Proc Natl Acad Sci U S A. 2000 Feb 01; 97(3):1096-100. View Abstract
Clathrin. Annu Rev Biochem. 2000; 69:699-727. View Abstract
Studies on the inhibition of endosome fusion by GTPgammaS-bound ARF. J Cell Sci. 1999 Oct; 112 ( Pt 20):3477-85. View Abstract
Cytolytic T lymphocyte-associated antigen-4 and the TCR zeta/CD3 complex, but not CD28, interact with clathrin adaptor complexes AP-1 and AP-2. J Immunol. 1999 Aug 15; 163(4):1868-79. View Abstract
Functional organization of clathrin in coats: combining electron cryomicroscopy and X-ray crystallography. Mol Cell. 1999 Jun; 3(6):761-70. View Abstract
The interaction between N-WASP and the Arp2/3 complex links Cdc42-dependent signals to actin assembly. Cell. 1999 Apr 16; 97(2):221-31. View Abstract
Cell biology. Boa constrictor or rattlesnake? Nature. 1999 Apr 08; 398(6727):470-1. View Abstract
Adaptors for clathrin-mediated traffic. Annu Rev Cell Dev Biol. 1999; 15:705-32. View Abstract
Atomic structure of clathrin: a beta propeller terminal domain joins an alpha zigzag linker. Cell. 1998 Nov 13; 95(4):563-73. View Abstract
Vesicle formation: dynamic dynamin lives up to its name. Curr Biol. 1998 Nov 05; 8(22):R792-4. View Abstract
A dileucine motif in HIV-1 Nef is essential for sorting into clathrin-coated pits and for downregulation of CD4. Curr Biol. 1998 Nov 05; 8(22):1239-42. View Abstract
A putative vacuolar cargo receptor partially colocalizes with AtPEP12p on a prevacuolar compartment in Arabidopsis roots. Proc Natl Acad Sci U S A. 1998 Aug 18; 95(17):9920-5. View Abstract
The clathrin endocytic pathway in viral infection. EMBO J. 1998 Aug 17; 17(16):4585-93. View Abstract
The neural cell adhesion molecule L1 interacts with the AP-2 adaptor and is endocytosed via the clathrin-mediated pathway. J Neurosci. 1998 Jul 15; 18(14):5311-21. View Abstract
Wiskott-Aldrich syndrome: a gene, a multifunctional protein and the beginnings of an explanation. Mol Med Today. 1998 Jul; 4(7):300-4. View Abstract
Dileucine-based sorting signals bind to the beta chain of AP-1 at a site distinct and regulated differently from the tyrosine-based motif-binding site. EMBO J. 1998 Apr 15; 17(8):2148-55. View Abstract
Assembly of clathrin coats disrupts the association between Eps15 and AP-2 adaptors. J Biol Chem. 1998 Jan 23; 273(4):1847-50. View Abstract
Interaction of the bovine papillomavirus E6 protein with the clathrin adaptor complex AP-1. J Virol. 1998 Jan; 72(1):476-82. View Abstract
Parallel dimers and anti-parallel tetramers formed by epidermal growth factor receptor pathway substrate clone 15. J Biol Chem. 1997 Dec 26; 272(52):33430-4. View Abstract
Linking cargo to vesicle formation: receptor tail interactions with coat proteins. Curr Opin Cell Biol. 1997 Aug; 9(4):488-95. View Abstract
Membranes and sorting. Membrane permeability. Curr Opin Cell Biol. 1997 Jul 01; 9(4):473. View Abstract
A role for the hinge/ear domain of the beta chains in the incorporation of AP complexes into clathrin-coated pits and coated vesicles. Cell Mol Life Sci. 1997 Jul; 53(7):611-9. View Abstract
Regulatory interactions in the recognition of endocytic sorting signals by AP-2 complexes. EMBO J. 1997 May 01; 16(9):2240-50. View Abstract
Eps15 is a component of clathrin-coated pits and vesicles and is located at the rim of coated pits. J Biol Chem. 1996 Nov 15; 271(46):28727-30. View Abstract
Sequence requirements for the recognition of tyrosine-based endocytic signals by clathrin AP-2 complexes. EMBO J. 1996 Nov 01; 15(21):5789-95. View Abstract
Identification of Itk/Tsk Src homology 3 domain ligands. J Biol Chem. 1996 Oct 11; 271(41):25646-56. View Abstract
Mechanisms of signal-mediated protein sorting in the endocytic and secretory pathways. Proc Assoc Am Physicians. 1996 Jul; 108(4):285-95. View Abstract
Disease mechanism: unravelling Wiskott-Aldrich syndrome. Curr Biol. 1996 Jun 01; 6(6):676-8. View Abstract
Direct interaction of the Wiskott-Aldrich syndrome protein with the GTPase Cdc42. Proc Natl Acad Sci U S A. 1996 May 28; 93(11):5615-8. View Abstract
Wortmannin alters the transferrin receptor endocytic pathway in vivo and in vitro. Mol Biol Cell. 1996 Mar; 7(3):355-67. View Abstract
A clathrin-binding site in the hinge of the beta 2 chain of mammalian AP-2 complexes. J Biol Chem. 1995 Dec 29; 270(52):31083-90. View Abstract
Role of the regulatory domain of the EGF-receptor cytoplasmic tail in selective binding of the clathrin-associated complex AP-2. Curr Biol. 1995 Oct 01; 5(10):1168-78. View Abstract
Interaction of tyrosine-based sorting signals with clathrin-associated proteins. Science. 1995 Sep 29; 269(5232):1872-5. View Abstract
Saccharomyces cerevisiae Apl2p, a homologue of the mammalian clathrin AP beta subunit, plays a role in clathrin-dependent Golgi functions. J Cell Sci. 1995 Apr; 108 ( Pt 4):1605-15. View Abstract
Molecular characterization of an apical early endosomal glycoprotein from developing rat intestinal epithelial cells. J Biol Chem. 1995 Jan 27; 270(4):1583-8. View Abstract
Stoichiometric interaction of the epidermal growth factor receptor with the clathrin-associated protein complex AP-2. J Biol Chem. 1995 Jan 13; 270(2):619-25. View Abstract
A late Golgi sorting function for Saccharomyces cerevisiae Apm1p, but not for Apm2p, a second yeast clathrin AP medium chain-related protein. Mol Biol Cell. 1995 Jan; 6(1):41-58. View Abstract
A rab protein is required for the assembly of SNARE complexes in the docking of transport vesicles. Cell. 1994 Sep 23; 78(6):937-48. View Abstract
The Saccharomyces cerevisiae APS1 gene encodes a homolog of the small subunit of the mammalian clathrin AP-1 complex: evidence for functional interaction with clathrin at the Golgi complex. EMBO J. 1994 Apr 01; 13(7):1706-17. View Abstract
Arrangement of domains, and amino acid residues required for binding of vascular cell adhesion molecule-1 to its counter-receptor VLA-4 (alpha 4 beta 1). J Cell Biol. 1994 Feb; 124(4):601-8. View Abstract
The beta 1 and beta 2 subunits of the AP complexes are the clathrin coat assembly components. EMBO J. 1993 Dec 15; 12(13):5237-44. View Abstract
Immunoelectron microscopic evidence for the extended conformation of light chains in clathrin trimers. J Biol Chem. 1993 May 15; 268(14):10268-73. View Abstract
Location of the domains of ICAM-1 by immunolabeling and single-molecule electron microscopy. J Leukoc Biol. 1993 Mar; 53(3):342-6. View Abstract
The medium chains of the mammalian clathrin-associated proteins have a homolog in yeast. Eur J Biochem. 1991 Dec 05; 202(2):569-74. View Abstract
AP17 and AP19, the mammalian small chains of the clathrin-associated protein complexes show homology to Yap17p, their putative homolog in yeast. J Biol Chem. 1991 Jun 15; 266(17):11153-7. View Abstract
Clathrin domains involved in recognition by assembly protein AP-2. J Biol Chem. 1991 Apr 25; 266(12):7950-6. View Abstract
Stabilization of clathrin coats by the core of the clathrin-associated protein complex AP-2. Biochemistry. 1990 Dec 04; 29(48):10791-8. View Abstract
Identification of a putative yeast homolog of the mammalian beta chains of the clathrin-associated protein complexes. Mol Cell Biol. 1990 Nov; 10(11):6089-90. View Abstract
Sequence of the rat alpha c large chain of the clathrin associated protein complex AP-2. Nucleic Acids Res. 1990 Sep 11; 18(17):5306. View Abstract
Analysis of clathrin light chain-heavy chain interactions using truncated mutants of rat liver light chain LCB3. J Biol Chem. 1990 Mar 05; 265(7):3661-8. View Abstract
Structural and functional division into two domains of the large (100- to 115-kDa) chains of the clathrin-associated protein complex AP-2. Proc Natl Acad Sci U S A. 1989 Apr; 86(8):2612-6. View Abstract
Molecular cloning and complete amino acid sequence of AP50, an assembly protein associated with clathrin-coated vesicles. DNA. 1988 Dec; 7(10):663-9. View Abstract
Clathrin heavy chain: molecular cloning and complete primary structure. Proc Natl Acad Sci U S A. 1987 Dec; 84(24):8805-9. View Abstract
Clathrin light chains LCA and LCB are similar, polymorphic, and share repeated heptad motifs. Science. 1987 Apr 17; 236(4799):320-4. View Abstract
Configuration of clathrin trimers: evidence from electron microscopy. J Ultrastruct Mol Struct Res. 1986 Mar; 94(3):199-208. View Abstract
Deep-etch views of clathrin assemblies. J Ultrastruct Res. 1985 Jul-Aug; 92(1-2):1-27. View Abstract
DNA gyrase and its complexes with DNA: direct observation by electron microscopy. Cell. 1985 Jul; 41(3):933-43. View Abstract
Structural domains of clathrin heavy chains. J Cell Biol. 1984 Nov; 99(5):1725-34. View Abstract
Divalent cation sites in tomato bushy stunt virus. Difference maps at 2-9 A resolution. J Mol Biol. 1983 Nov 25; 171(1):95-100. View Abstract
Clathrin, cages, and coated vesicles. Cell. 1983 Jul; 33(3):650-2. View Abstract
Location and distribution of the light chains in clathrin trimers. Proc Natl Acad Sci U S A. 1983 May; 80(9):2481-5. View Abstract
Thermal effects in human plasma high density lipoproteins (HDL)3: a 13C-FT-NMR study. Acta Cient Venez. 1983; 34(3-4):209-15. View Abstract
Serum low density lipoproteins with mitogenic effect on cultured aortic smooth muscle cells. Atherosclerosis. 1982 Feb; 41(2-3):171-83. View Abstract
Protein organization in clathrin trimers. Cell. 1981 Mar; 23(3):755-61. View Abstract
The structure of plasma low density lipoproteins: experimental facts and interpretations--a minireview. Lipids. 1980 Jun; 15(6):464-7. View Abstract
Atherogenic diets and neutral-lipid organization in plasma low density lipoproteins. Atherosclerosis. 1979 May; 33(1):59-70. View Abstract
Kinetics of thermal transitions in human serum low density lipoproteins (LDL) and neutral lipids. A dynamic small-angle X-ray scattering study. Acta Cient Venez. 1979; 30(5):478-83. View Abstract
Small-angle X-ray scattering and differential scanning calorimetry studies on reversibly modified human-serum low density lipoproteins. Biochemistry. 1978 Apr 18; 17(8):1436-40. View Abstract
A low temperature structural transition in human serum low density lipoproteins. Biochim Biophys Acta. 1977 Apr 26; 487(1):243-5. View Abstract
Small-angle x-ray scattering study of human serum low-density lipoproteins with differential reactivity for an arterial proteoglycan. J Supramol Struct. 1977; 7(3-4):435-42. View Abstract

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