Recruitment of endophilin to clathrin-coated pit necks is required for efficient vesicle uncoating after fission. Neuron 2011 Nov 17;72(4):587-601
Date
11/22/2011Pubmed ID
22099461Pubmed Central ID
PMC3258500DOI
10.1016/j.neuron.2011.08.029Scopus ID
2-s2.0-81355153885 (requires institutional sign-in at Scopus site) 277 CitationsAbstract
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.
Author List
Milosevic I, Giovedi S, Lou X, Raimondi A, Collesi C, Shen H, Paradise S, O'Toole E, Ferguson S, Cremona O, De Camilli PAuthor
Xuelin Lou PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adaptor Proteins, Signal TransducingAnimals
Cell Division
Cell Membrane
Clathrin
Clathrin-Coated Vesicles
Coated Pits, Cell-Membrane
Intracellular Signaling Peptides and Proteins
Mice
Mice, Knockout
Models, Neurological
Protein Transport
Rats
Synapses
