Drosophila α- and β-Spectrin Mutations Disrupt Presynaptic Neurotransmitter Release

By D. Featherstone, W. Davis, R. Dubreuil, K. Broadie. Journal of Neuroscience, 2001

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Spectrins are plasma membrane-associated cytoskeletal proteins implicated in several aspects of synaptic development and function, including presynaptic vesicle tethering and postsynaptic receptor aggregation. To test these hypotheses, we characterizedDrosophila mutants lacking either α- or β-spectrin. The Drosophila genome contains only one α-spectrin and one conventional β-spectringene, making it an ideal system to genetically manipulate spectrin levels and examine the resulting synaptic alterations. Both spectrin proteins are strongly expressed in theDrosophila neuromusculature and highly enriched at the glutamatergic neuromuscular junction. Protein null α- and β-spectrin mutants are embryonic lethal and display severely disrupted neurotransmission without altered morphological synaptogenesis. Contrary to current models, the absence of spectrins does not alter postsynaptic glutamate receptor field function or the ultrastructural localization of presynaptic vesicles. However, the subcellular localization of numerous synaptic proteins is disrupted, suggesting that the defects in presynaptic neurotransmitter release may be attributable to inappropriate assembly, transport, or localization of proteins required for synaptic function.

Subfields: Cell Biology, Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/4fdc2c7de752a7503f9c5d908c9a6af258f6c3ea