Compromised fidelity of endocytic synaptic vesicle protein sorting in the absence of stonin 2.
Neurotransmission depends on the exocytic fusion of synaptic vesicles (SVs) and their subsequent reformation either by clathrin-mediated endocytosis or budding from bulk endosomes. How synapses are able to rapidly recycle SVs to maintain SV pool size, yet preserve their compositional identity, is poorly understood. We demonstrate that deletion of the endocytic adaptor stonin 2 (Stn2) in mice compromises the fidelity of SV protein sorting, whereas the apparent speed of SV retrieval is increased. Loss of Stn2 leads to selective missorting of synaptotagmin 1 to the neuronal surface, an elevated SV pool size, and accelerated SV protein endocytosis. The latter phenotype is mimicked by overexpression of endocytosis-defective variants of synaptotagmin 1. Increased speed of SV protein retrieval in the absence of Stn2 correlates with an up-regulation of SV reformation from bulk endosomes. Our results are consistent with a model whereby Stn2 is required to preserve SV protein composition but is dispensable for maintaining the speed of SV recycling.
Department of Molecular Pharmacology and Cell Biology, Leibniz Institut für Molekulare Pharmakologie, 13125 Berlin,  Germany.
Natalia L
NL
Kononenko
M Kasim
MK
Diril
Dmytro
D
Puchkov
Michael
M
Kintscher
Seong Joo
SJ
Koo
Gerit
G
Pfuhl
York
Y
Winter
Martin
M
Wienisch
Jürgen
J
Klingauf
Jörg
J
Breustedt
Dietmar
D
Schmitz
Tanja
T
Maritzen
Volker
V
Haucke
D033942:Adaptor Proteins, Vesicular Transport / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity; D021381:Protein Transport; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D016708:Synaptophysin / Q000378:metabolism; D050863:Synaptotagmin I / Q000235:genetics / Q000378:metabolism; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism
D033942:Adaptor Proteins, Vesicular Transport; D009419:Nerve Tissue Proteins; D016708:Synaptophysin; D050863:Synaptotagmin I; C569015:Syp protein, mouse; C494311:Syt1 protein, mouse; D050988:Vesicle-Associated Membrane Protein 2; C579576:stonin 2 protein, mouse; C494808:vesicle-associated membrane protein 2, mouse