Endophilin/SH3p4 is required for the transition from early to late stages in clathrin-mediated synaptic vesicle endocytosis.
Endophilin/SH3p4 is a protein highly enriched in nerve terminals that binds the GTPase dynamin and the polyphosphoinositide phosphatase synaptojanin, two proteins implicated in synaptic vesicle endocytosis. We show here that antibody-mediated disruption of endophilin function in a tonically stimulated synapse leads to a block in the invagination of clathrin-coated pits adjacent to the active zone and therefore to a block of synaptic vesicle recycling. We also show that in a cell-free system, endophilin is not associated with clathrin coats and is a functional partner of dynamin. Our findings suggest that endophilin is part of a biochemical machinery that acts in trans to the clathrin coat from early stages to vesicle fission.
Ringstad
N
N
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Gad
H
H
Löw
P
P
Di Paolo
G
G
Brodin
L
L
Shupliakov
O
O
De Camilli
P
P
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017173:Caenorhabditis elegans / Q000235:genetics; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D002474:Cell-Free System; D002966:Clathrin / Q000502:physiology*; D003034:Coated Pits, Cell-Membrane / Q000502:physiology*; D034281:Dynamins; D004705:Endocytosis; D020558:GTP Phosphohydrolases / Q000502:physiology; D007798:Lampreys; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D051381:Rats; D013116:Spinal Cord / Q000737:chemistry; D013569:Synapses / Q000648:ultrastructure; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; D002352:Carrier Proteins; D002966:Clathrin; D020558:GTP Phosphohydrolases; D034281:Dynamins