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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.

Original publication

DOI

10.1016/j.neuron.2011.08.029

Type

Journal article

Journal

Neuron

Publication Date

11/2011

Volume

72

Pages

587 - 601

Addresses

Department of Cell Biology, Howard Hughes Medical Institute, Program in Cellular Neuroscience, Neurodegeneration, and Repair, Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT 06519, USA.

Keywords

Synapses, Cell Membrane, Coated Pits, Cell-Membrane, Clathrin-Coated Vesicles, Animals, Mice, Knockout, Mice, Rats, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Clathrin, Cell Division, Protein Transport, Models, Neurological