An autoinhibitory clamp of actin assembly constrains and directs synaptic endocytosis

eLife

Markus Mund¹  Marko Kaksonen¹  Charlotte F Kelley²  Tania Lemos²  Emily M Messelaar²  Biljana Ermanoska²  Michelle F Marchan²  Steven J Del Signore²  Avital Adah Rodal²  Thomas G Fai³ 

[1] Department of Biochemistry and NCCR Chemical Biology, University of Geneva, Geneva, Switzerland;Department of Biology, Brandeis University, Walltham, United States;Department of Mathematics, Brandeis University, Waltham, United States;

关键词: synapse;    endocytosis;    actin;    D. melanogaster;   

DOI  :  10.7554/eLife.69597

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY