Interaction of stoned and synaptotagmin in synaptic vesicle endocytosis

Citation
T. Fergestad et K. Broadie, Interaction of stoned and synaptotagmin in synaptic vesicle endocytosis, J NEUROSC, 21(4), 2001, pp. 1218-1227
Citations number
52
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROSCIENCE
ISSN journal
0270-6474 → ACNP
Volume
21
Issue
4
Year of publication
2001
Pages
1218 - 1227
Database
ISI
SICI code
0270-6474(20010215)21:4<1218:IOSASI>2.0.ZU;2-J
Abstract
The Drosophila dicistronic stoned locus encodes two distinctive presynaptic proteins, Stoned A (STNA) and Stoned B (STNB); STNA is a novel protein wit hout homology to known synaptic proteins, and STNB contains a domain with h omology to the endocytotic protein AP50. Both Stoned proteins colocalize pr ecisely with endocytotic proteins including the AP2 complex and Dynamin in the "lattice network" characteristic of endocytotic domains in Drosophila p resynaptic terminals. FM1-43 dye uptake studies in stoned mutants demonstra te a striking decrease in the size of the endo-exo-cycling synaptic vesicle pool and loss of spatial regulation of the vesicular recycling intermediat es. Mutant synapses display a significant delay in vesicular membrane retri eval after depolarization and neurotransmitter release. These studies sugge st that the Stoned proteins play a role in mediating synaptic vesicle endoc ytosis. We have documented previously a highly specific synaptic mislocaliz ation and degradation of Synaptotagmin I in stoned mutants. Here we show th at transgenic overexpression of Synaptotagmin I rescues stoned embryonic le thality and restores endocytotic recycling to normal levels. Furthermore, o verexpression of Synaptotagmin I in otherwise wild-type animals results in increased synaptic dye uptake, indicating that Synaptotagmin I directly reg ulates the endo-exo-cycling synaptic vesicle pool size. In parallel with re cent biochemical studies, this genetic analysis strongly suggests that Ston ed proteins regulate the AP2-Synaptotagmin I interaction during synaptic ve sicle endocytosis. We conclude that Stoned proteins control synaptic transm ission strength by mediating the retrieval of Synaptotagmin I from the plas ma membrane.