Interaction of the ERC Family of RIM-binding Proteins with the Liprin-α Family of Multidomain Proteins

Abstract

Liprin-α/SYD-2 is a family of multidomain proteins with four known isoforms. One of the reported functions of liprin-α is to regulate the development of presynaptic active zones, but the underlying mechanism is poorly understood. Here we report that liprin-α directly interacts 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-α and that liprin-α1 associates with both ERC2 and ERC1b, a splice variant of ERC1 that distributes to both cytosolic and active zone regions. ERC2 colocalizes with liprin-α1 in cultured neurons and forms a complex with liprin-α1 in brain. Liprin-α1, when expressed alone in cultured neurons, shows a partial synaptic localization. When coexpressed with ERC2, however, liprin-α is redistributed to synaptic sites. Moreover, roughly the first half of ERC2, which contains the liprin-α-binding region, is sufficient for the synaptic localization of liprin-α1 while the second half is not. These results suggest that the interaction between ERC2 and liprin-α may be involved in the presynaptic localization of liprin-α and the molecular organization of presynaptic active zones.