Redundant Localization Mechanisms of RIM and ELKS inCaenorhabditis elegans

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Abstract
Active zone proteins play a fundamental role in regulating neurotransmitter release and defining release sites. The functional roles of active zone components are beginning to be elucidated; however, the mechanisms of active zone protein localization are unknown. Studies have shown that glutamine, leucine, lysine, and serine-rich protein (ELKS), a recently defined member of the active zone complex, acts to localize the active zone protein Rab3a-interacting molecule (RIM) and regulates synaptic transmission in cultured neurons. Here, we test the function of ELKSin vivo. Like mammalian ELKS,Caenorhabditis elegansELKS is an active zone protein that directly interacts with the postsynaptic density-25/Discs large/zona occludens (PDZ) domain of RIM. However, RIM protein localizes in the absence of ELKS andvice versa. In addition,elksmutants exhibit neither the behavioral nor the physiological defects associated withunc-10RIM mutants, indicating that ELKS is not a critical component of theC. elegansrelease machinery. Interestingly, expression of the soluble PDZ domain of RIM disrupts ELKS active zone targeting, suggesting a tight association between the two proteinsin vivo. RIM truncations containing only the PDZ and C2A domains target to release sites in an ELKS-dependent manner. Together, these data identify ELKS as a new member of theC. elegansactive zone complex, define the role of ELKS in synaptic transmission, and characterize the relationship between ELKS and RIMin vivo. Furthermore, they demonstrate that multiple different protein-protein interactions redundantly anchor both ELKS and RIM to active zones and implicate novel proteins in the formation of the active zone.