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Science 328 (5983): 1281-1284

Copyright © 2010 by the American Association for the Advancement of Science

FCHo Proteins Are Nucleators of Clathrin-Mediated Endocytosis

William Mike Henne,*,{dagger} Emmanuel Boucrot,{dagger},{ddagger} Michael Meinecke, Emma Evergren, Yvonne Vallis, Rohit Mittal, Harvey T. McMahon{ddagger}

Abstract: Clathrin-mediated endocytosis, the major pathway for ligand internalization into eukaryotic cells, is thought to be initiated by the clustering of clathrin and adaptors around receptors destined for internalization. However, here we report that the membrane-sculpting F-BAR domain–containing Fer/Cip4 homology domain-only proteins 1 and 2 (FCHo1/2) were required for plasma membrane clathrin-coated vesicle (CCV) budding and marked sites of CCV formation. Changes in FCHo1/2 expression levels correlated directly with numbers of CCV budding events, ligand endocytosis, and synaptic vesicle marker recycling. FCHo1/2 proteins bound specifically to the plasma membrane and recruited the scaffold proteins eps15 and intersectin, which in turn engaged the adaptor complex AP2. The FCHo F-BAR membrane-bending activity was required, leading to the proposal that FCHo1/2 sculpt the initial bud site and recruit the clathrin machinery for CCV formation.

Medical Research Council, Laboratory of Molecular Biology (MRC-LMB), Hills Road, Cambridge CB2 0QH, UK.

* Present address: Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA.

{dagger} These authors contributed equally to this work.

{ddagger} To whom correspondence should be addressed. E-mail: hmm{at} (H.T.M); eboucrot{at} (E.B.)

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A. C. Humphries, S. K. Donnelly, and M. Way (2014)
J. Cell Sci. 127, 673-685
   Abstract »    Full Text »    PDF »
Bending "On the Rocks"--A Cocktail of Biophysical Modules to Build Endocytic Pathways.
L. Johannes, C. Wunder, and P. Bassereau (2014)
Cold Spring Harb Perspect Biol 6, a016741
   Abstract »    Full Text »    PDF »
Linear aggregation of proteins on the membrane as a prelude to membrane remodeling.
M. Simunovic, A. Srivastava, and G. A. Voth (2013)
PNAS 110, 20396-20401
   Abstract »    Full Text »    PDF »
From uncertain beginnings: Initiation mechanisms of clathrin-mediated endocytosis.
C. Godlee and M. Kaksonen (2013)
J. Cell Biol. 203, 717-725
   Abstract »    Full Text »    PDF »
LMBD1 Protein Serves as a Specific Adaptor for Insulin Receptor Internalization.
L. T.-L. Tseng, C.-L. Lin, K.-Y. Tzen, S. C. Chang, and M.-F. Chang (2013)
J. Biol. Chem. 288, 32424-32432
   Abstract »    Full Text »    PDF »
Endocytosis of EGFR requires its kinase activity and N-terminal transmembrane dimerization motif.
R. Heukers, J. F. Vermeulen, F. Fereidouni, A. N. Bader, J. Voortman, R. C. Roovers, H. C. Gerritsen, and P. M. P. van Bergen en Henegouwen (2013)
J. Cell Sci. 126, 4900-4912
   Abstract »    Full Text »    PDF »
Cargo Recognition in Clathrin-Mediated Endocytosis.
L. M. Traub and J. S. Bonifacino (2013)
Cold Spring Harb Perspect Biol 5, a016790
   Abstract »    Full Text »    PDF »
Regulation of ubiquitin-dependent cargo sorting by multiple endocytic adaptors at the plasma membrane.
J. R. Mayers, L. Wang, J. Pramanik, A. Johnson, A. Sarkeshik, Y. Wang, W. Saengsawang, J. R. Yates III, and A. Audhya (2013)
PNAS 110, 11857-11862
   Abstract »    Full Text »    PDF »
Fast neurotransmitter release regulated by the endocytic scaffold intersectin.
T. Sakaba, N. L. Kononenko, J. Bacetic, A. Pechstein, J. Schmoranzer, L. Yao, H. Barth, O. Shupliakov, O. Kobler, K. Aktories, et al. (2013)
PNAS 110, 8266-8271
   Abstract »    Full Text »    PDF »
Cooperative Recruitment of Dynamin and BIN/Amphiphysin/Rvs (BAR) Domain-containing Proteins Leads to GTP-dependent Membrane Scission.
M. Meinecke, E. Boucrot, G. Camdere, W.-C. Hon, R. Mittal, and H. T. McMahon (2013)
J. Biol. Chem. 288, 6651-6661
   Abstract »    Full Text »    PDF »
The dynamin-binding domains of Dap160/intersectin affect bulk membrane retrieval in synapses.
A. M. E. Winther, W. Jiao, O. Vorontsova, K. A. Rees, T.-W. Koh, E. Sopova, K. L. Schulze, H. J. Bellen, and O. Shupliakov (2013)
J. Cell Sci. 126, 1021-1031
   Abstract »    Full Text »    PDF »
Caenorhabditis elegans reveals a FxNPxY-independent low-density lipoprotein receptor internalization mechanism mediated by epsin1.
Y.-L. Kang, J. Yochem, L. Bell, E. B. Sorensen, L. Chen, and S. D. Conner (2013)
Mol. Biol. Cell 24, 308-318
   Abstract »    Full Text »    PDF »
Role of Phospholipids in Endocytosis, Phagocytosis, and Macropinocytosis.
M. Bohdanowicz and S. Grinstein (2013)
Physiol Rev 93, 69-106
   Abstract »    Full Text »    PDF »
Dynamics of clathrin-mediated endocytosis and its requirement for organelle biogenesis in Dictyostelium.
L. Macro, J. K. Jaiswal, and S. M. Simon (2012)
J. Cell Sci. 125, 5721-5732
   Abstract »    Full Text »    PDF »
PSTPIP2 deficiency in mice causes osteopenia and increased differentiation of multipotent myeloid precursors into osteoclasts.
V. Chitu, V. Nacu, J. F. Charles, W. M. Henne, H. T. McMahon, S. Nandi, H. Ketchum, R. Harris, M. C. Nakamura, and E. R. Stanley (2012)
Blood 120, 3126-3135
   Abstract »    Full Text »    PDF »
Synaptic Vesicle Endocytosis.
Y. Saheki and P. De Camilli (2012)
Cold Spring Harb Perspect Biol 4, a005645
   Abstract »    Full Text »    PDF »
The clathrin adaptor Dab2 recruits EH domain scaffold proteins to regulate integrin {beta}1 endocytosis.
A. Teckchandani, E. E. Mulkearns, T. W. Randolph, N. Toida, and J. A. Cooper (2012)
Mol. Biol. Cell 23, 2905-2916
   Abstract »    Full Text »    PDF »
Acute depletion of plasma membrane phosphatidylinositol 4,5-bisphosphate impairs specific steps in endocytosis of the G-protein-coupled receptor.
D. J. Toth, J. T. Toth, G. Gulyas, A. Balla, T. Balla, L. Hunyady, and P. Varnai (2012)
J. Cell Sci. 125, 2185-2197
   Abstract »    Full Text »    PDF »
FCH domain only-2 organizes clathrin-coated structures and interacts with Disabled-2 for low-density lipoprotein receptor endocytosis.
E. E. Mulkearns and J. A. Cooper (2012)
Mol. Biol. Cell 23, 1330-1342
   Abstract »    Full Text »    PDF »
Intersectin 1 Enhances Cbl Ubiquitylation of Epidermal Growth Factor Receptor through Regulation of Sprouty2-Cbl Interaction.
M. N. Okur, J. Ooi, C. W. Fong, N. Martinez, C. Garcia-Dominguez, J. M. Rojas, G. Guy, and J. P. O'Bryan (2012)
Mol. Cell. Biol. 32, 817-825
   Abstract »    Full Text »    PDF »
Analysis of yeast endocytic site formation and maturation through a regulatory transition point.
S. Y. Carroll, H. E. M. Stimpson, J. Weinberg, C. P. Toret, Y. Sun, and D. G. Drubin (2012)
Mol. Biol. Cell 23, 657-668
   Abstract »    Full Text »    PDF »
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T.-C. Chao, W.-C. Su, J.-Y. Huang, Y.-C. Chen, K.-S. Jeng, H.-D. Wang, and M. M. C. Lai (2012)
J. Virol. 86, 1739-1749
   Abstract »    Full Text »    PDF »
Endocytosis and Signaling: Cell Logistics Shape the Eukaryotic Cell Plan.
S. Sigismund, S. Confalonieri, A. Ciliberto, S. Polo, G. Scita, and P. P. Di Fiore (2012)
Physiol Rev 92, 273-366
   Abstract »    Full Text »    PDF »
Proper synaptic vesicle formation and neuronal network activity critically rely on syndapin I.
D. Koch, I. Spiwoks-Becker, V. Sabanov, A. Sinning, T. Dugladze, A. Stellmacher, R. Ahuja, J. Grimm, S. Schuler, A. Muller, et al. (2011)
EMBO J. 30, 4955-4969
   Abstract »    Full Text »    PDF »
Determinants of endocytic membrane geometry, stability, and scission.
T. Kishimoto, Y. Sun, C. Buser, J. Liu, A. Michelot, and D. G. Drubin (2011)
PNAS 108, E979-E988
   Abstract »    Full Text »    PDF »
Let's go bananas: revisiting the endocytic BAR code.
B. Qualmann, D. Koch, and M. M. Kessels (2011)
EMBO J. 30, 3501-3515
   Abstract »    Full Text »    PDF »
Phosphatidylinositol-(4,5)-bisphosphate regulates clathrin-coated pit initiation, stabilization, and size.
C. N. Antonescu, F. Aguet, G. Danuser, and S. L. Schmid (2011)
Mol. Biol. Cell 22, 2588-2600
   Abstract »    Full Text »    PDF »
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Y. Senju, Y. Itoh, K. Takano, S. Hamada, and S. Suetsugu (2011)
J. Cell Sci. 124, 2032-2040
   Abstract »    Full Text »    PDF »
Harvey McMahon: Ahead of the curve on membrane dynamics.
B. Short (2011)
J. Cell Biol. 193, 598-599
   Full Text »    PDF »
Endocytic adaptors - social networking at the plasma membrane.
A. Reider and B. Wendland (2011)
J. Cell Sci. 124, 1613-1622
   Abstract »    Full Text »    PDF »
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K. Rajalingam and F. G. van der Goot (2011)
EMBO Rep. 12, 188-190
   Full Text »    PDF »
Negative Regulation of the Endocytic Adaptor Disabled-2 (Dab2) in Mitosis.
D. Chetrit, L. Barzilay, G. Horn, T. Bielik, N. I. Smorodinsky, and M. Ehrlich (2011)
J. Biol. Chem. 286, 5392-5403
   Abstract »    Full Text »    PDF »
INTERSECTINg Pathways in Cell Biology.
J. P. O'Bryan (2010)
Science Signaling 3, re10
   Abstract »    Full Text »    PDF »
Genome-Wide mRNA and microRNA Profiling of the NCI 60 Cell-Line Screen and Comparison of FdUMP[10] with Fluorouracil, Floxuridine, and Topoisomerase 1 Poisons.
W. H. Gmeiner, W. C. Reinhold, and Y. Pommier (2010)
Mol. Cancer Ther. 9, 3105-3114
   Abstract »    Full Text »    PDF »
Quantitative Analysis of the Mechanism of Endocytic Actin Patch Assembly and Disassembly in Fission Yeast.
V. Sirotkin, J. Berro, K. Macmillan, L. Zhao, and T. D. Pollard (2010)
Mol. Biol. Cell 21, 2894-2904
   Abstract »    Full Text »    PDF »
The inositol 5-phosphatase SHIP2 regulates endocytic clathrin-coated pit dynamics.
F. Nakatsu, R. M. Perera, L. Lucast, R. Zoncu, J. Domin, F. B. Gertler, D. Toomre, and P. De Camilli (2010)
J. Cell Biol. 190, 307-315
   Abstract »    Full Text »    PDF »

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