title: Splicing factors control C. elegans behavioural learning in a single neuron by producing DAF-2c receptor.
abstract: Alternative splicing generates protein diversity essential for neuronal properties. However, the precise mechanisms underlying this process and its relevance to physiological and behavioural functions are poorly understood. To address these issues, we focused on a cassette exon of the Caenorhabditis elegans insulin receptor gene daf-2, whose proper variant expression in the taste receptor neuron ASER is critical for taste-avoidance learning. We show that inclusion of daf-2 exon 11.5 is restricted to specific neuron types, including ASER, and is controlled by a combinatorial action of evolutionarily conserved alternative splicing factors, RBFOX, CELF and PTB families of proteins. Mutations of these factors cause a learning defect, and this defect is relieved by DAF-2c (exon 11.5+) isoform expression only in a single neuron ASER. Our results provide evidence that alternative splicing regulation of a single critical gene in a single critical neuron is essential for learning ability in an organism.
authors.affiliation: Molecular Genetics Research Laboratory, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tomioka
authors.affiliation: Molecular Genetics Research Laboratory, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.|Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Naito
authors.affiliation: Laboratory of Gene Expression, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Hidehito
authors.initials: H
authors.lastname: Kuroyanagi
authors.affiliation: Molecular Genetics Research Laboratory, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.|Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Iino
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002628:Chemoreceptor Cells / Q000378:metabolism*; D000072670:PTB-Associated Splicing Factor / Q000235:genetics / Q000378:metabolism*; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D000072670:PTB-Associated Splicing Factor; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin