Wbox2: A clathrin terminal domain-derived peptide inhibitor of clathrin-mediated endocytosis.

The Journal of Cell Biology
Zhiming ChenSandra L Schmid

Abstract

Clathrin-mediated endocytosis (CME) occurs via the formation of clathrin-coated vesicles from clathrin-coated pits (CCPs). Clathrin is recruited to CCPs through interactions between the AP2 complex and its N-terminal domain, which in turn recruits endocytic accessory proteins. Inhibitors of CME that interfere with clathrin function have been described, but their specificity and mechanisms of action are unclear. Here we show that overexpression of the N-terminal domain with (TDD) or without (TD) the distal leg inhibits CME and CCP dynamics by perturbing clathrin interactions with AP2 and SNX9. TDD overexpression does not affect clathrin-independent endocytosis or, surprisingly, AP1-dependent lysosomal trafficking from the Golgi. We designed small membrane-permeant peptides that encode key functional residues within the four known binding sites on the TD. One peptide, Wbox2, encoding residues along the W-box motif binding surface, binds to SNX9 and AP2 and potently and acutely inhibits CME.

References

Sep 1, 1991·The Journal of Cell Biology·S L Schmid, E Smythe
Jan 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·B M Pearse
Mar 1, 1981·Cell·T Kirchhausen, S C Harrison
Jan 29, 1981·Nature·E Ungewickell, D Branton
Dec 29, 1995·The Journal of Biological Chemistry·W ShihT Kirchhausen
Nov 15, 1996·The Journal of Biological Chemistry·H OhnoJ S Bonifacino
Aug 4, 1999·Proceedings of the National Academy of Sciences of the United States of America·L M TraubD H Fremont
Feb 3, 2000·Proceedings of the National Academy of Sciences of the United States of America·E ter HaarT Kirchhausen
Aug 16, 2000·The EMBO Journal·D J OwenP R Evans
Aug 8, 2001·Trends in Cell Biology·E C Dell'Angelica
Nov 1, 2001·Annual Review of Cell and Developmental Biology·F M BrodskyD E Wakeham
Jan 25, 2002·The Journal of Cell Biology·Andrew A PedenMargaret S Robinson
Sep 4, 2003·The Journal of Cell Biology·Sean D Conner, Sandra L Schmid
Feb 26, 2004·Nature Structural & Molecular Biology·Adriana E MieleDavid J Owen
Oct 22, 2004·The EMBO Journal·Gerrit J K PraefckeHarvey T McMahon
Feb 4, 2005·Molecular Biology of the Cell·Howard S MoskowitzTimothy A Ryan
May 16, 2006·Cellular and Molecular Life Sciences : CMLS·S J Royle
Sep 21, 2006·Journal of Cell Science·Meghan E Maurer, Jonathan A Cooper
Jun 22, 2007·The EMBO Journal·Peter MichaelyJonathan C Cohen
Aug 24, 2007·Nature·Eva M Schmid, Harvey T McMahon
Jul 22, 2008·Nature Methods·Khuloud JaqamanGaudenz Danuser
Aug 28, 2009·The Journal of Biological Chemistry·Dong Soo KangJeffrey L Benovic
Nov 26, 2010·The Journal of Biological Chemistry·Rafael MatteraJuan S Bonifacino
Jan 14, 2012·Traffic·Sandra K Lemmon, Linton M Traub
Aug 7, 2012·Cell·Emanuele CocucciTom Kirchhausen
Oct 3, 2012·PloS One·Dipannita DuttaJulie G Donaldson
Sep 21, 2013·Journal of Cell Science·Ryan J ParkPietro De Camilli
Nov 5, 2013·Cold Spring Harbor Perspectives in Biology·Linton M Traub, Juan S Bonifacino

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Citations

Aug 10, 2020·The Journal of Cell Biology·Zhiming Chen, Sandra L Schmid
Dec 2, 2020·Proceedings of the National Academy of Sciences of the United States of America·Madhura BhaveMarcel Mettlen
Aug 25, 2020·Current Opinion in Cell Biology·Kit BriantFrances M Brodsky

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Datasets Mentioned

BETA
GM-130

Methods Mentioned

BETA
fluorescence microscopy
immunoprecipitation
coIPs
coimmunoprecipitation
pull-down
pulldown
protein folding
FACS
transfection
ELISA

Software Mentioned

SEDPHAT
GenScript
cmeAnalysis
ImageJ

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