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Cell ; 174(4): 884-896.e17, 2018 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-30057119

RESUMO

Clathrin-mediated endocytosis is an essential cellular function in all eukaryotes that is driven by a self-assembled macromolecular machine of over 50 different proteins in tens to hundreds of copies. How these proteins are organized to produce endocytic vesicles with high precision and efficiency is not understood. Here, we developed high-throughput superresolution microscopy to reconstruct the nanoscale structural organization of 23 endocytic proteins from over 100,000 endocytic sites in yeast. We found that proteins assemble by radially ordered recruitment according to function. WASP family proteins form a circular nanoscale template on the membrane to spatially control actin nucleation during vesicle formation. Mathematical modeling of actin polymerization showed that this WASP nano-template optimizes force generation for membrane invagination and substantially increases the efficiency of endocytosis. Such nanoscale pre-patterning of actin nucleation may represent a general design principle for directional force generation in membrane remodeling processes such as during cell migration and division.


Assuntos
Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Endocitose/fisiologia , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Vesículas Secretórias/metabolismo , Família de Proteínas da Síndrome de Wiskott-Aldrich/metabolismo , Actinas/química , Membrana Celular/metabolismo , Microscopia de Fluorescência , Modelos Teóricos , Conformação Proteica , Família de Proteínas da Síndrome de Wiskott-Aldrich/química
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