CASK stabilizes neurexin and links it to liprin-? in a neuronal activity-dependent manner.

ABSTRACT: CASK, a MAGUK family protein, is an essential protein present in the presynaptic compartment. CASK's cellular role is unknown, but it interacts with multiple proteins important for synapse formation and function, including neurexin, liprin-?, and Mint1. CASK phosphorylates neurexin in a divalent ion-sensitive manner, although the functional relevance of this activity is unclear. Here we find that liprin-? and Mint1 compete for direct binding to CASK, but neurexin1? eliminates this competition, and all four proteins form a complex. We describe a novel mode of interaction between liprin-? and CASK when CASK is bound to neurexin1?. We show that CASK phosphorylates neurexin, modulating the interaction of liprin-? with the CASK-neurexin1?-Mint1 complex. Thus, CASK creates a regulatory and structural link between the presynaptic adhesion molecule neurexin and active zone organizer, liprin-?. In neuronal culture, CASK appears to regulate the stability of neurexin by linking it with this multi-protein presynaptic active zone complex.

SUBMITTER: LaConte LE 

PROVIDER: S-EPMC4982824 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature