title: CASY-1, an ortholog of calsyntenins/alcadeins, is essential for learning in Caenorhabditis elegans.
abstract: Calsyntenins/alcadeins are type I transmembrane proteins with two extracellular cadherin domains highly expressed in mammalian brain. They form a tripartite complex with X11/X11L and APP (amyloid precursor protein) and are proteolytically processed in a similar fashion to APP. Although a genetic association of calsyntenin-2 with human memory performance has recently been reported, physiological roles and molecular functions of the protein in the nervous system are poorly understood. Here, we show that CASY-1, the Caenorhabditis elegans ortholog of calsyntenins/alcadeins, is essential for multiple types of learning. Through a genetic screen, we found that casy-1 mutants show defects in salt chemotaxis learning. casy-1 mutants also show defects in temperature learning, olfactory adaptation, and integration of two sensory signals. casy-1 is widely expressed in the nervous system. Expression of casy-1 in a single sensory neuron and at the postdevelopmental stage is sufficient for its function in salt chemotaxis learning. The fluorescent protein-tagged ectodomain of CASY-1 is released from neurons. Moreover, functional domain analyses revealed that both cytoplasmic and transmembrane domains of this protein are dispensable, whereas the ectodomain, which contains the LG/LNS-like domain, is critically required for learning. These results suggest that learning is modulated by the released ectodomain of CASY-1.
authors.affiliation: Molecular Genetics Research Laboratory and Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Daisuke D
authors.initials: DD
authors.lastname: Ikeda
authors.forename: Yukan
authors.initials: Y
authors.lastname: Duan
authors.forename: Masahiro
authors.initials: M
authors.lastname: Matsuki
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kunitomo
authors.forename: Harald
authors.initials: H
authors.lastname: Hutter
authors.forename: Edward M
authors.initials: EM
authors.lastname: Hedgecock
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Iino
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002633:Chemotaxis / Q000187:drug effects; D007328:Insulin / Q000378:metabolism; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D015398:Signal Transduction; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: C528269:CASY-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D007328:Insulin; D012965:Sodium Chloride