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Wbox2: A clathrin terminal domain–derived peptide inhibitor of clathrin-mediated endocytosis
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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480105/ https://www.ncbi.nlm.nih.gov/pubmed/32520988 http://dx.doi.org/10.1083/jcb.201908189 |
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author | Chen, Zhiming Mino, Rosa E. Mettlen, Marcel Michaely, Peter Bhave, Madhura Reed, Dana Kim Schmid, Sandra L. |
author_facet | Chen, Zhiming Mino, Rosa E. Mettlen, Marcel Michaely, Peter Bhave, Madhura Reed, Dana Kim Schmid, Sandra L. |
author_sort | Chen, Zhiming |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7480105 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-74801052020-09-21 Wbox2: A clathrin terminal domain–derived peptide inhibitor of clathrin-mediated endocytosis Chen, Zhiming Mino, Rosa E. Mettlen, Marcel Michaely, Peter Bhave, Madhura Reed, Dana Kim Schmid, Sandra L. J Cell Biol Article 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. Rockefeller University Press 2020-06-10 /pmc/articles/PMC7480105/ /pubmed/32520988 http://dx.doi.org/10.1083/jcb.201908189 Text en © 2020 Chen et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chen, Zhiming Mino, Rosa E. Mettlen, Marcel Michaely, Peter Bhave, Madhura Reed, Dana Kim Schmid, Sandra L. Wbox2: A clathrin terminal domain–derived peptide inhibitor of clathrin-mediated endocytosis |
title | Wbox2: A clathrin terminal domain–derived peptide inhibitor of clathrin-mediated endocytosis |
title_full | Wbox2: A clathrin terminal domain–derived peptide inhibitor of clathrin-mediated endocytosis |
title_fullStr | Wbox2: A clathrin terminal domain–derived peptide inhibitor of clathrin-mediated endocytosis |
title_full_unstemmed | Wbox2: A clathrin terminal domain–derived peptide inhibitor of clathrin-mediated endocytosis |
title_short | Wbox2: A clathrin terminal domain–derived peptide inhibitor of clathrin-mediated endocytosis |
title_sort | wbox2: a clathrin terminal domain–derived peptide inhibitor of clathrin-mediated endocytosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480105/ https://www.ncbi.nlm.nih.gov/pubmed/32520988 http://dx.doi.org/10.1083/jcb.201908189 |
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