Role of Drosophila Rab5 during endosomal trafficking at the synapse and evoked neurotransmitter release.
During constitutive endocytosis, internalized membrane traffics through endosomal compartments. At synapses, endocytosis of vesicular membrane is temporally coupled to action potential-induced exocytosis of synaptic vesicles. Endocytosed membrane may immediately be reused for a new round of neurotransmitter release without trafficking through an endosomal compartment. Using GFP-tagged endosomal markers, we monitored an endosomal compartment in Drosophila neuromuscular synapses. We showed that in conditions in which the synaptic vesicles pool is depleted, the endosome is also drastically reduced and only recovers from membrane derived by dynamin-mediated endocytosis. This suggests that membrane exchange takes place between the vesicle pool and the synaptic endosome. We demonstrate that the small GTPase Rab5 is required for endosome integrity in the presynaptic terminal. Impaired Rab5 function affects endo- and exocytosis rates and decreases the evoked neurotransmitter release probability. Conversely, Rab5 overexpression increases the release efficacy. Therefore, the Rab5-dependent trafficking pathway plays an important role for synaptic performance.
Max-Planck Institut für Molekulare Zellbiologie und Genetik, Dresden, Germany.
Tanja
T
Wucherpfennig
Michaela
M
Wilsch-Bräuninger
Marcos
M
González-Gaitán
D000818:Animals; D002451:Cell Compartmentation / Q000235:genetics; D004331:Drosophila melanogaster / Q000378:metabolism* / Q000648:ultrastructure; D004705:Endocytosis / Q000235:genetics*; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure; D005089:Exocytosis / Q000235:genetics; D007150:Immunohistochemistry; D008561:Membrane Fusion / Q000235:genetics; D008854:Microscopy, Electron; D009154:Mutation / Q000235:genetics; D009469:Neuromuscular Junction / Q000378:metabolism* / Q000648:ultrastructure; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010243:Paralysis / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D021381:Protein Transport / Q000235:genetics*; D013570:Synaptic Membranes / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics; D013572:Synaptic Vesicles / Q000378:metabolism / Q000648:ultrastructure; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D018377:Neurotransmitter Agents; D020696:rab5 GTP-Binding Proteins