title: Loss of skywalker reveals synaptic endosomes as sorting stations for synaptic vesicle proteins.
abstract: Exchange of proteins at sorting endosomes is not only critical to numerous signaling pathways but also to receptor-mediated signaling and to pathogen entry into cells; however, how this process is regulated in synaptic vesicle cycling remains unexplored. In this work, we present evidence that loss of function of a single neuronally expressed GTPase activating protein (GAP), Skywalker (Sky) facilitates endosomal trafficking of synaptic vesicles at Drosophila neuromuscular junction boutons, chiefly by controlling Rab35 GTPase activity. Analyses of genetic interactions with the ESCRT machinery as well as chimeric ubiquitinated synaptic vesicle proteins indicate that endosomal trafficking facilitates the replacement of dysfunctional synaptic vesicle components. Consequently, sky mutants harbor a larger readily releasable pool of synaptic vesicles and show a dramatic increase in basal neurotransmitter release. Thus, the trafficking of vesicles via endosomes uncovered using sky mutants provides an elegant mechanism by which neurons may regulate synaptic vesicle rejuvenation and neurotransmitter release.
authors: VIB, Department of Molecular and Developmental Genetics, Program in Molecular and Developmental Genetics, Program in Cognitive and Molecular Neuroscience, Laboratory of Neuronal Communication, Herestraat 49, 3000 Leuven, Belgium.
authors: Valerie
authors: V
authors: Uytterhoeven
authors: Sabine
authors: S
authors: Kuenen
authors: Jaroslaw
authors: J
authors: Kasprowicz
authors: Katarzyna
authors: K
authors: Miskiewicz
authors: Patrik
authors: P
authors: Verstreken
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D009154:Mutation; D009420:Nervous System / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D018377:Neurotransmitter Agents; C558398:sky protein, Drosophila; D020691:rab GTP-Binding Proteins