Eps15 and Dap160 control synaptic vesicle membrane retrieval and synapse development.
Epidermal growth factor receptor pathway substrate clone 15 (Eps15) is a protein implicated in endocytosis, endosomal protein sorting, and cytoskeletal organization. Its role is, however, still unclear, because of reasons including limitations of dominant-negative experiments and apparent redundancy with other endocytic proteins. We generated Drosophila eps15-null mutants and show that Eps15 is required for proper synaptic bouton development and normal levels of synaptic vesicle (SV) endocytosis. Consistent with a role in SV endocytosis, Eps15 moves from the center of synaptic boutons to the periphery in response to synaptic activity. The endocytic protein, Dap160/intersectin, is a major binding partner of Eps15, and eps15 mutants phenotypically resemble dap160 mutants. Analyses of eps15 dap160 double mutants suggest that Eps15 functions in concert with Dap160 during SV endocytosis. Based on these data, we hypothesize that Eps15 and Dap160 promote the efficiency of endocytosis from the plasma membrane by maintaining high concentrations of multiple endocytic proteins, including dynamin, at synapses.
Koh
Tong-Wey
TW
Graduate Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Korolchuk
Viktor I
VI
Wairkar
Yogesh P
YP
Jiao
Wei
W
Evergren
Emma
E
Pan
Hongling
H
Zhou
Yi
Y
Venken
Koen J T
KJ
Shupliakov
Oleg
O
Robinson
Iain M
IM
O'Kane
Cahir J
CJ
Bellen
Hugo J
HJ
D000818:Animals; D004330:Drosophila / Q000235:genetics / Q000254:growth & development; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D004705:Endocytosis / Q000502:physiology; D007150:Immunohistochemistry; D007814:Larva / Q000254:growth & development / Q000648:ultrastructure; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D013572:Synaptic Vesicles / Q000502:physiology* / Q000648:ultrastructure; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure
C113692:Dap160 protein, Drosophila; D029721:Drosophila Proteins; C512908:Eps-15 protein, Drosophila; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D033921:Vesicular Transport Proteins