Interaction of the ERC family of RIMbinding proteins with the liprin-alpha family of multidomain proteins

Liprin-/SYD-2 is a family of multidomain proteins with four known isoforms. One of the reported functions of liprin- is to regulate the development of presynaptic active zones, but the underlying mechanism is poorly understood. Here we report that liprin- directly inter-acts with the ERC (ELKS-Rab6-interacting protein-CAST) family of proteins, members of which are known to bind RIMs, the active zone proteins that regulate neurotransmitter release. In vitro results indicate that ERC2/CAST, an active zone-specific isoform, interacts with all of the known isoforms of liprin- and that lip-rin-1 associates with both ERC2 and ERC1b, a splice variant of ERC1 that distributes to both cytosolic and active zone regions. ERC2 colocalizes with liprin-1 in cultured neurons and forms a complex with liprin-1 i