The cadherin domains and the kinesin-binding intracellular domain of CASY-1/calsyntenin function in a redundant manner for learning

Taste avoidance learning in <i>Caenorhabditis elegans</i> is regulated by the calsyntenin/alcadein homolog CASY-1 , which transports the insulin receptor DAF-2c to the synaptic region. This transport involves binding of the CASY-1 intracellular domain to the kinesin-1 (KIF5) complex. However, a previous study showed that the intracellular domain of CASY-1 is dispensable for learning. To investigate how CASY-1 functions, we performed functional domain mapping of CASY-1 . Both the cadherin domains of CASY-1 and its binding to kinesin-1 are individually dispensable, while simultaneous loss of both abolished the CASY-1 function, suggesting that CASY-1 enables robust intracellular transport through physical interactions with multiple proteins.