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Recruitment of endophilin to clathrin-coated pit necks is required for efficient vesicle uncoating after fission.

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.

Pubmed ID: 22099461

Authors

  • Milosevic I
  • Giovedi S
  • Lou X
  • Raimondi A
  • Collesi C
  • Shen H
  • Paradise S
  • O'Toole E
  • Ferguson S
  • Cremona O
  • De Camilli P

Journal

Neuron

Publication Data

November 17, 2011

Associated Grants

  • Agency: NIDA NIH HHS, Id: DA018343
  • Agency: NIDDK NIH HHS, Id: DK45735
  • Agency: Telethon, Id: GGP10099
  • Agency: NINDS NIH HHS, Id: NS36251
  • Agency: NIDA NIH HHS, Id: P30 DA018343
  • Agency: NIDA NIH HHS, Id: P30 DA018343-09
  • Agency: NIDDK NIH HHS, Id: P30 DK045735
  • Agency: NIDDK NIH HHS, Id: P30 DK045735-14
  • Agency: NCRR NIH HHS, Id: P41 RR000592
  • Agency: NCRR NIH HHS, Id: P41 RR000592-40
  • Agency: NINDS NIH HHS, Id: R01 NS036251
  • Agency: NINDS NIH HHS, Id: R01 NS036251-13
  • Agency: NINDS NIH HHS, Id: R37 NS036251
  • Agency: NCRR NIH HHS, Id: RR-000592

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • 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