Drosophila alpha- and beta-spectrin mutations disrupt presynaptic neurotransmitter release.
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 characterized Drosophila mutants lacking either alpha- or beta-spectrin. The Drosophila genome contains only one alpha-spectrin and one conventional beta-spectrin gene, making it an ideal system to genetically manipulate spectrin levels and examine the resulting synaptic alterations. Both spectrin proteins are strongly expressed in the Drosophila neuromusculature and highly enriched at the glutamatergic neuromuscular junction. Protein null alpha- and beta-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.
Featherstone
D E
DE
Department of Biology, University of Utah, Salt Lake City, Utah 84112-0840, USA.
Davis
W S
WS
Dubreuil
R R
RR
Broadie
K
K
D000818:Animals; D002135:Calcium-Binding Proteins; D004330:Drosophila; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000294:innervation; D005804:Genes, Lethal; D018698:Glutamic Acid / Q000494:pharmacology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007814:Larva; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008565:Membrane Proteins / Q000096:biosynthesis; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009469:Neuromuscular Junction / Q000187:drug effects / Q000196:embryology / Q000378:metabolism* / Q000648:ultrastructure; D018377:Neurotransmitter Agents / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D050765:Qa-SNARE Proteins; D013049:Spectrin / Q000096:biosynthesis / Q000235:genetics*; D016704:Synapsins / Q000096:biosynthesis; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism / Q000648:ultrastructure; D050857:Synaptotagmins
D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D050765:Qa-SNARE Proteins; D016704:Synapsins; D013049:Spectrin; D050857:Synaptotagmins; D018698:Glutamic Acid