title: Regulation of Fasciclin II and synaptic terminal development by the splicing factor beag.
abstract: Pre-mRNA alternative splicing is an important mechanism for the generation of synaptic protein diversity, but few factors governing this process have been identified. From a screen for Drosophila mutants with aberrant synaptic development, we identified beag, a mutant with fewer synaptic boutons and decreased neurotransmitter release. Beag encodes a spliceosomal protein similar to splicing factors in humans and Caenorhabditis elegans. We find that both beag mutants and mutants of an interacting gene dsmu1 have changes in the synaptic levels of specific splice isoforms of Fasciclin II (FasII), the Drosophila ortholog of neural cell adhesion molecule. We show that restoration of one splice isoform of FasII can rescue synaptic morphology in beag mutants while expression of other isoforms cannot. We further demonstrate that this FasII isoform has unique functions in synaptic development independent of transsynaptic adhesion. beag and dsmu1 mutants demonstrate an essential role for these previously uncharacterized splicing factors in the regulation of synapse development and function.
authors.affiliation: Center for Motor Neuron Biology and Disease, Department of Pathology and Cell Biology and Department of Neuroscience, Columbia University Medical Center, New York, New York 10032, USA.
authors.forename: Erin S
authors.initials: ES
authors.lastname: Beck
authors.forename: Gabriel
authors.initials: G
authors.lastname: Gasque
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Imlach
authors.forename: Wei
authors.initials: W
authors.lastname: Jiao
authors.forename: Ben
authors.initials: B
authors.lastname: Jiwon Choi
authors.forename: Pao-Shu
authors.initials: PS
authors.lastname: Wu
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Kraushar
authors.forename: Brian D
authors.initials: BD
authors.lastname: McCabe
mesh_terms: D017398:Alternative Splicing / Q000235:genetics / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009154:Mutation; D009469:Neuromuscular Junction / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D017729:Presynaptic Terminals / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017381:Spliceosomes / Q000378:metabolism
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D029721:Drosophila Proteins; D020033:Protein Isoforms; C051642:fasciclin II