Expression and Function of Munc13 Proteins in the Mammalian Retina

Abstract

Abstract: : Purpose: Munc13-1, 13-2 and 13-3 comprise a family of proteins that are essential for vesicle priming at synapses. Mice deficient in Munc13-1 lack glutamatergic synaptic transmission and are not viable. We examined the expression and synaptic localization of the three Munc13 proteins in the wild-type retina, and analysed the structure and function of the retinae of Munc13-2 and Munc13-3 deletion mutant mice. Methods: Munc13 mRNA expression and protein localization was examined in wild-type retina by in situ hybridization and immunocytochemistry, respectively. Structure and function of retinae of Munc13 deletion mutant mice was studied by immunocytochemistry and recordings of ERGs. Results: Whereas all neurons of the retina seemed to express Munc13-1 mRNA, subsets of bipolar and amacrine cells expressed Munc13-2 and Munc13-3 mRNA, and expression was mutually exclusive. Immunocytochemistry localized Munc13-1 presynaptically at photoreceptor and amacrine cell synapses and postsynaptically in dendrites and processes of bipolar and horizontal cells, respectively. Munc13-1 was absent at bipolar cell synapses. This was also true for Munc13-3, whose expression was restricted to amacrine cell synapses and to bipolar cell dendrites. The structure and function of the retinae of Munc13-2 and Munc13-3 deletion mutant mice appeared normal. Conclusions: The three Munc13 proteins are heterogeneously expressed at retinal synapses. Photoreceptor ribbon synapses express only Munc13-1, amacrine cell synapses express combinations of Munc13-1/13-2 or Munc13-1/13-3, and bipolar cell ribbon synapses appear not to express any of the three Munc13 proteins. In addition to presynaptic localization, we also identified a postsynaptic site of action of Munc13 proteins at retinal synapses. As the lack of Munc13-2 and Munc13-3 in deletion mutant mice has no obvious effect on the structure and function of the retina, Munc13-1 is the key functional Munc13 protein at retinal synapses.

Keywords: synapse • retina • signal transduction