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An autoinhibitory clamp of actin assembly constrains and directs synaptic endocytosis
Synaptic membrane-remodeling events such as endocytosis require force-generating actin assembly. The endocytic machinery that regulates these actin and membrane dynamics localizes at high concentrations to large areas of the presynaptic membrane, but actin assembly and productive endocytosis are far...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321554/ https://www.ncbi.nlm.nih.gov/pubmed/34324418 http://dx.doi.org/10.7554/eLife.69597 |
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author | Del Signore, Steven J Kelley, Charlotte F Messelaar, Emily M Lemos, Tania Marchan, Michelle F Ermanoska, Biljana Mund, Markus Fai, Thomas G Kaksonen, Marko Rodal, Avital Adah |
author_facet | Del Signore, Steven J Kelley, Charlotte F Messelaar, Emily M Lemos, Tania Marchan, Michelle F Ermanoska, Biljana Mund, Markus Fai, Thomas G Kaksonen, Marko Rodal, Avital Adah |
author_sort | Del Signore, Steven J |
collection | PubMed |
description | Synaptic membrane-remodeling events such as endocytosis require force-generating actin assembly. The endocytic machinery that regulates these actin and membrane dynamics localizes at high concentrations to large areas of the presynaptic membrane, but actin assembly and productive endocytosis are far more restricted in space and time. Here we describe a mechanism whereby autoinhibition clamps the presynaptic endocytic machinery to limit actin assembly to discrete functional events. We found that collective interactions between the Drosophila endocytic proteins Nwk/FCHSD2, Dap160/intersectin, and WASp relieve Nwk autoinhibition and promote robust membrane-coupled actin assembly in vitro. Using automated particle tracking to quantify synaptic actin dynamics in vivo, we discovered that Nwk-Dap160 interactions constrain spurious assembly of WASp-dependent actin structures. These interactions also promote synaptic endocytosis, suggesting that autoinhibition both clamps and primes the synaptic endocytic machinery, thereby constraining actin assembly to drive productive membrane remodeling in response to physiological cues. |
format | Online Article Text |
id | pubmed-8321554 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-83215542021-07-30 An autoinhibitory clamp of actin assembly constrains and directs synaptic endocytosis Del Signore, Steven J Kelley, Charlotte F Messelaar, Emily M Lemos, Tania Marchan, Michelle F Ermanoska, Biljana Mund, Markus Fai, Thomas G Kaksonen, Marko Rodal, Avital Adah eLife Cell Biology Synaptic membrane-remodeling events such as endocytosis require force-generating actin assembly. The endocytic machinery that regulates these actin and membrane dynamics localizes at high concentrations to large areas of the presynaptic membrane, but actin assembly and productive endocytosis are far more restricted in space and time. Here we describe a mechanism whereby autoinhibition clamps the presynaptic endocytic machinery to limit actin assembly to discrete functional events. We found that collective interactions between the Drosophila endocytic proteins Nwk/FCHSD2, Dap160/intersectin, and WASp relieve Nwk autoinhibition and promote robust membrane-coupled actin assembly in vitro. Using automated particle tracking to quantify synaptic actin dynamics in vivo, we discovered that Nwk-Dap160 interactions constrain spurious assembly of WASp-dependent actin structures. These interactions also promote synaptic endocytosis, suggesting that autoinhibition both clamps and primes the synaptic endocytic machinery, thereby constraining actin assembly to drive productive membrane remodeling in response to physiological cues. eLife Sciences Publications, Ltd 2021-07-29 /pmc/articles/PMC8321554/ /pubmed/34324418 http://dx.doi.org/10.7554/eLife.69597 Text en © 2021, Del Signore et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Del Signore, Steven J Kelley, Charlotte F Messelaar, Emily M Lemos, Tania Marchan, Michelle F Ermanoska, Biljana Mund, Markus Fai, Thomas G Kaksonen, Marko Rodal, Avital Adah An autoinhibitory clamp of actin assembly constrains and directs synaptic endocytosis |
title | An autoinhibitory clamp of actin assembly constrains and directs synaptic endocytosis |
title_full | An autoinhibitory clamp of actin assembly constrains and directs synaptic endocytosis |
title_fullStr | An autoinhibitory clamp of actin assembly constrains and directs synaptic endocytosis |
title_full_unstemmed | An autoinhibitory clamp of actin assembly constrains and directs synaptic endocytosis |
title_short | An autoinhibitory clamp of actin assembly constrains and directs synaptic endocytosis |
title_sort | autoinhibitory clamp of actin assembly constrains and directs synaptic endocytosis |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321554/ https://www.ncbi.nlm.nih.gov/pubmed/34324418 http://dx.doi.org/10.7554/eLife.69597 |
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