Tetanus neurotoxin sensitive SNARE-mediated glial signaling limits motoneuronal excitability

Abstract

Peripheral nerves contain motoneuron axons coated by glial cells, which essentially contribute to nerve function. How glial cells communicate with other cells and whether secretion or SNARE-mediated fusion reactions are involved remains poorly understood. We here report on essential SNARE-mediated reactions in distinct glial subtypes of Drosophila peripheral nerves that establish insulating septate junctions (SJ) and provide metabolic support to neuronal axons. Interference with these reactions by glial expression of the proposedly neurospecific tetanus neurotoxin light chain caused nerve disintegration, interfered with axonal transport, induced tetanic muscle hyperactivity and lethal paralysis. We identify non-neuronal Synaptobrevin as the relevant vesicular SNARE protein and link its function to two glial subtypes that differentially contribute to SJ formation (subperineurial glia) and neural metabolic support (wrapping glia). Our study thus identifies a crucial role of SNARE-mediated reactions in glial subtypes for nerve function and pathology, animal motility and survival.