Drosophila alpha- and beta-spectrin mutations disrupt presynaptic neurotransmitter release

Spectrins are plasma membrane-associated cytoskeletal proteins implicated i n several aspects of synaptic development and function, including presynapt ic vesicle tethering and postsynaptic receptor aggregation. To test these h ypotheses, we characterized Drosophila mutants lacking either alpha- or bet a -spectrin. The Drosophila genome contains only one alpha -spectrin and on e conventional beta -spectrin gene, making it an ideal system to geneticall y manipulate spectrin levels and examine the resulting synaptic alterations . Both spectrin proteins are strongly expressed in the Drosophila neuromusc ulature and highly enriched at the glutamatergic neuromuscular junction. Pr otein null alpha- and beta -spectrin mutants are embryonic lethal and displ ay severely disrupted neurotransmission without altered morphological synap togenesis. Contrary to current models, the absence of spectrins does not al ter postsynaptic glutamate receptor field function or the ultrastructural l ocalization 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 a ssembly, transport, or localization of proteins required for synaptic funct ion.