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


RESULTS
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.


CONCLUSIONS
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.
Hoerndli
Frédéric J
FJ
Institute of Zoology, University of Zürich, Zürich, Switzerland.
Walser
Michael
M
Fröhli Hoier
Erika
E
de Quervain
Dominique
D
Papassotiropoulos
Andreas
A
Hajnal
Alex
A
D000818:Animals; D001522:Behavior, Animal; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007858:Learning / Q000502:physiology*; D009154:Mutation; D018091:Receptors, AMPA / Q000502:physiology
C528269:CASY-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D018091:Receptors, AMPA; C096470:glr-1 protein, C elegans