An autoinhibitory clamp of actin assembly constrains and directs synaptic endocytosis release_d62czd3uhzcjhlg7iyegcrugmu

by Steven J Del Signore, Charlotte Kelley, Emily M Messelaar, Tania Eskin, Michelle F Marchan, Biljana Ermanoska, Markus Mund, Thomas Fai, Marko Kaksonen, Avital Rodal

Published in eLife by eLife Sciences Publications, Ltd.

2021   Volume 10

Abstract

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 <jats:italic>Drosophila</jats:italic> 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.
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Type  article-journal
Stage   published
Date   2021-07-29
Language   en ?
DOI  10.7554/elife.69597
PubMed  34324418
PMC  PMC8321554
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