RRC ID 4245
Author Ikeda DD, Duan Y, Matsuki M, Kunitomo H, Hutter H, Hedgecock EM, Iino Y.
Title CASY-1, an ortholog of calsyntenins/alcadeins, is essential for learning in Caenorhabditis elegans.
Journal Proc. Natl. Acad. Sci. U.S.A.
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.
Volume 105(13)
Pages 5260-5
Published 2008-4-1
DOI 10.1073/pnas.0711894105
PII 105/13/5260
PMID 18381821
PMC PMC2278220
MeSH Animals Caenorhabditis elegans / cytology Caenorhabditis elegans / drug effects Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Chemotaxis / drug effects Insulin / metabolism Learning / drug effects Learning / physiology* Mutation / genetics Neurons / metabolism Signal Transduction Sodium Chloride / pharmacology
IF 9.504
Times Cited 38
C.elegans tm718