The RIM1 mutation associated with an autosomal dominant cone-rod dystrophy, CORD7, alters effects of RIM1 on VDCC currents

Abstract

Recent genetic analyses have revealed an important association of the gene encoding the Rab3A-interacting molecule (RIM1) with CORD7, an autosomal dominant cone-rod dystrophy. However, the effects of RIM1 mutation which associated with CORD7 have remained unclear. Recently we have revealed effects of RIM1 on VDCC currents, anchoring of neurotransmitter-containing vesicles and neurotransmitter release. In this study, we demonstrate that the mouse RIM1 arginine-to-histidine substitution R655H, which corresponds to human CORD7 mutation, impaires RIM1 function in ACh release and regulation of VDCC currents. Thus, we suggest that phenotypes of familial cone-rod dystrophy with RIM1 mutation can be at least partly attributable to defects in regulation of presynaptic VDCC currents, presumably resulting in retinal deficits. [J Physiol Sci. 2008;58 Suppl:S74]