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...
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doaj-c44cbbc7f83f475d9d26d4dd000baafa2021-07-29T16:03:09ZengeLife Sciences Publications LtdeLife2050-084X2021-07-011010.7554/eLife.69597An autoinhibitory clamp of actin assembly constrains and directs synaptic endocytosisSteven J Del Signore0https://orcid.org/0000-0001-6007-9732Charlotte F Kelley1https://orcid.org/0000-0002-7684-9049Emily M Messelaar2Tania Lemos3https://orcid.org/0000-0002-6710-7676Michelle F Marchan4Biljana Ermanoska5Markus Mund6https://orcid.org/0000-0001-6449-743XThomas G Fai7https://orcid.org/0000-0003-0383-5217Marko Kaksonen8https://orcid.org/0000-0003-3645-7689Avital Adah Rodal9https://orcid.org/0000-0002-2051-8304Department of Biology, Brandeis University, Walltham, United StatesDepartment of Biology, Brandeis University, Walltham, United StatesDepartment of Biology, Brandeis University, Walltham, United StatesDepartment of Biology, Brandeis University, Walltham, United StatesDepartment of Biology, Brandeis University, Walltham, United StatesDepartment of Biology, Brandeis University, Walltham, United StatesDepartment of Biochemistry and NCCR Chemical Biology, University of Geneva, Geneva, SwitzerlandDepartment of Mathematics, Brandeis University, Waltham, United StatesDepartment of Biochemistry and NCCR Chemical Biology, University of Geneva, Geneva, SwitzerlandDepartment of Biology, Brandeis University, Walltham, United StatesSynaptic 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.https://elifesciences.org/articles/69597synapseendocytosisactin |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Steven J Del Signore Charlotte F Kelley Emily M Messelaar Tania Lemos Michelle F Marchan Biljana Ermanoska Markus Mund Thomas G Fai Marko Kaksonen Avital Adah Rodal |
spellingShingle |
Steven J Del Signore Charlotte F Kelley Emily M Messelaar Tania Lemos Michelle F Marchan Biljana Ermanoska Markus Mund Thomas G Fai Marko Kaksonen Avital Adah Rodal An autoinhibitory clamp of actin assembly constrains and directs synaptic endocytosis eLife synapse endocytosis actin |
author_facet |
Steven J Del Signore Charlotte F Kelley Emily M Messelaar Tania Lemos Michelle F Marchan Biljana Ermanoska Markus Mund Thomas G Fai Marko Kaksonen Avital Adah Rodal |
author_sort |
Steven J Del Signore |
title |
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_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_sort |
autoinhibitory clamp of actin assembly constrains and directs synaptic endocytosis |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2021-07-01 |
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. |
topic |
synapse endocytosis actin |
url |
https://elifesciences.org/articles/69597 |
work_keys_str_mv |
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