Stathmin is required for stability of the Drosophila neuromuscular junction.
Synaptic connections can be stably maintained for prolonged periods, yet can be rapidly disassembled during the developmental refinement of neural circuitry and following cytological insults that lead to neurodegeneration. To date, the molecular mechanisms that determine whether a synapse will persist versus being remodeled or eliminated remain poorly understood. Mutations in Drosophila stathmin were isolated in two independent genetic screens that sought mutations leading to impaired synapse stability at the Drosophila neuromuscular junction (NMJ). Here we demonstrate that Stathmin, a protein that associates with microtubules and can function as a point of signaling integration, is necessary to maintain the stability of the Drosophila NMJ. We show that Stathmin protein is widely distributed within motoneurons and that loss of Stathmin causes impaired NMJ growth and stability. In addition, we show that stathmin mutants display evidence of defective axonal transport, a common feature associated with neuronal degeneration and altered synapse stability. The disassembly of the NMJ in stathmin includes a predictable sequence of cytological events, suggesting that a common program of synapse disassembly is induced following the loss of Stathmin protein. These data define a required function for Stathmin during synapse maintenance in a model system in which there is only a single stathmin gene, enabling future genetic investigation of Stathmin function with potential relevance to the cause and progression of neuromuscular degenerative disease.
Department of Biology and Neuroscience Program, Amherst College, Amherst, Massachusetts 01002, USA.
Ethan R
ER
Graf
Heather M
HM
Heerssen
Christina M
CM
Wright
Graeme W
GW
Davis
Aaron
A
DiAntonio
D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D009154:Mutation / Q000235:genetics; D009469:Neuromuscular Junction / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D017729:Presynaptic Terminals / Q000378:metabolism; D034622:RNA Interference / Q000502:physiology; D050777:Stathmin / Q000235:genetics / Q000378:metabolism*; D050496:Vesicular Glutamate Transport Proteins / Q000235:genetics
C510146:BRP protein, Drosophila; D029721:Drosophila Proteins; D050777:Stathmin; D050496:Vesicular Glutamate Transport Proteins