A conserved function of C. elegans CASY-1 calsyntenin in associative learning

• Published in: PloS one 2009-03, Vol.4 (3), p.e4880-e4880
• Main Authors: Hoerndli, Frédéric J, Walser, Michael, Fröhli Hoier, Erika, de Quervain, Dominique, Papassotiropoulos, Andreas, Hajnal, Alex
• Format: Article
• Language: English
• Subjects: Animals; Associative learning; Behavior; Behavior, Animal; Caenorhabditis elegans; Caenorhabditis elegans - physiology; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - physiology; Cognitive ability; Conservation; Drosophila melanogaster; Genes; Genetic aspects; Genetic polymorphisms; Genetics; Genetics and Genomics; Genetics and Genomics/Gene Discovery; Genetics and Genomics/Gene Function; Genome-wide association studies; Genomes; Genomics; Glutamate; Glutamic acid receptors; Human performance; Humans; Independent study; Insects; Learning; Learning - physiology; Memory; Metabolism; Mutants; Mutation; Nematodes; Neurons; Neuroscience; Neuroscience/Behavioral Neuroscience; Neuroscience/Neuronal Signaling Mechanisms; Proteins; Receptors, AMPA - physiology; Rodents; Roundworms; Signal transduction; Studies; Worms; Zebrafish; Zoology; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0004880

Whole-genome association studies in humans have enabled the unbiased discovery of new genes associated with human memory performance. However, such studies do not allow for a functional or causal testing of newly identified candidate genes. Since polymorphisms in Calsyntenin 2 (CLSTN2) showed a significant association with episodic memory performance in humans, we tested the C. elegans CLSTN2 ortholog CASY-1 for possible functions in the associative behavior of C. elegans. Using three different associative learning paradigms and functional rescue experiments, we show that CASY-1 plays an important role during associative learning in C. elegans. Furthermore, neuronal expression of human CLSTN2 in C. elegans rescues the learning defects of casy-1 mutants. Finally, genetic interaction studies and neuron-specific expression experiments suggest that CASY-1 may regulate AMPA-like GLR-1 glutamate receptor signaling. Our experiments demonstrate a remarkable conservation of the molecular function of Calsyntenins between nematodes and humans and point at a role of C. elegans casy-1 in regulating a glutamate receptor signaling pathway.