Recruitment of Endophilin to Clathrin-Coated Pit Necks Is Required for Efficient Vesicle Uncoating after Fission

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作者：

Ira Milosevic and Silvia Giovedi and Xuelin Lou and Andrea Raimondi and Chiara Collesi and Hongying Shen and Summer Paradise and Eileen O'Toole and Shawn Ferguson and Ottavio Cremona and Pietro De Camilli

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摘要：

Summary Endophilin is a membrane-binding protein with curvature-generating and -sensing properties that participates in clathrin-dependent endocytosis of synaptic vesicle membranes. Endophilin also binds the GTPase dynamin and the phosphoinositide phosphatase synaptojanin and is thought to coordinate constriction of coated pits with membrane fission (via dynamin) and subsequent uncoating (via synaptojanin). We show that although synaptojanin is recruited by endophilin at bud necks before fission, the knockout of all three mouse endophilins results in the accumulation of clathrin-coated vesicles, but not of clathrin-coated pits, at synapses. The absence of endophilin impairs but does not abolish synaptic transmission and results in perinatal lethality, whereas partial endophilin absence causes severe neurological defects, including epilepsy and neurodegeneration. Our data support a model in which endophilin recruitment to coated pit necks, because of its curvature-sensing properties, primes vesicle buds for subsequent uncoating after membrane fission, without being critically required for the fission reaction itself.

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关键词：

Antibodies Autoimmunity Multiple sclerosis Myelin Biomarkers

DOI：

10.1016/j.neuron.2011.08.029

被引量：

306

年份：

2011