Analysis of RIM Expression and Function at Mouse Photoreceptor Ribbon Synapses

RIM (RAB3A-interacting molecule) proteins are important regulators of transmitter release from active zones. At conventional chemical synapses, RIMs contribute substantially to vesicle priming and docking, and their loss reduces the readily releasable pool of synaptic vesicles by up to 75 %. The priming function of RIMs is mediated via the formation of a tripartite complex with Munc13 and RAB3A, which brings synaptic vesicles in close proximity to Ca 2+ channels and the fusion site, and activates Munc13. We reported previously that at mouse photoreceptor ribbon synapses vesicle priming is Munc13-independent. In this study, we examined RIM expression, distribution and function at male and female mouse photoreceptor ribbon synapses. We provide evidence that RIM1α and β are highly likely absent from mouse photoreceptors, and that RIM2α is the major large RIM isoform present at photoreceptor ribbon synapses. We show that mouse photoreceptors predominantly express RIM2 variants which lack the interaction domain for Munc13. Loss of full-length RIM2α in a RIM2α mutant mouse only marginally perturbs photoreceptor synaptic transmission. Our findings therefore strongly argue for a priming mechanism at the photoreceptor ribbon synapse that is independent of the formation of a RIM-Munc13-RAB3A complex, and thus provide further evidence for a fundamental difference between photoreceptor ribbon synapses and conventional chemical synapses in synaptic vesicle exocytosis. SIGNIFICANCE STATEMENT RIM1/2 are essential regulators of exocytosis. At conventional chemical synapses, their function involves Ca 2+ channel clustering, and synaptic vesicle priming and docking through interactions with Munc13 and RAB3A, respectively. Examining wild-type and RIM2 mutant mice we show here that the sensory photoreceptor ribbon synapses most likely lack RIM1 and predominantly express RIM2 variants that lack the interaction domain for Munc13. Our findings demonstrate that the photoreceptor-specific RIM variants are not essential for synaptic vesicle priming at photoreceptor ribbon synapses, which represents a fundamental difference between photoreceptor ribbon synapses and conventional chemical synapses with respect to synaptic vesicle priming mechanisms.