An autoinhibitory clamp of actin assembly constrains and directs synaptic endocytosis

Article Article scientifique Article An autoinhibitory clamp of actin assembly constrains and directs synaptic endocytosis eng 2021-07-29 2021-07-29 author Del Signore Steven J 0000-0001-6007-9732 author Kelley Charlotte F 0000-0002-7684-9049 author Messelaar Emily M author Lemos Tania 0000-0002-6710-7676 author Marchan Michelle F author Ermanoska Biljana 0000-0003-3913-8253 author Mund Markus 0000-0001-6449-743X 895738 author Fai Thomas G 0000-0003-0383-5217 author Kaksonen Marko 0000-0003-3645-7689 830048 author Rodal Avital Adah 0000-0002-2051-8304 e69597 10.7554/eLife.69597 34324418 2050-084X PMC8321554 https://elifesciences.org/articles/69597 <p> 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. </p> D. melanogaster Actin Cell biology Endocytosis Neuroscience Synapse Dewey 540 Swiss National Science Foundation Molecular mechanisms of clathrin-mediated endocytosis 310030B_182825 CH Project funding National Institutes of Health DA032435 Pew Charitable Trusts March of Dimes Foundation National Science Foundation NSF-DMR 2011846 39 Département de biochimie 144 false 1397 Groupe Kaksonen eLife 10 48c32ba4-949c-4ab4-b802-d5a785d7f7c4 Article (Published version) Public Article-scientifique-from-crossref.pdf 4577218 application/pdf openAccess Faculté des sciences / Section de chimie et biochimie / Département de biochimie

Title	Published in	Year	Views	Downloads

An autoinhibitory clamp of actin assembly constrains and directs synaptic endocytosis	eLife	2021	225	139
Type-I myosins promote actin polymerization to drive membrane bending in endocytosis	eLife	2019	354	311

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