Expression and modulation of connexin30.2, a novel gap junction protein in the mouse retina

Abstract

Mammalian retinae express multiple connexins that mediate the metabolic and electrical coupling of various cell types. In retinal neurons, only connexin 36, connexin 45, connexin 50, and connexin 57 have been described so far. Here, we present an analysis of a novel retinal connexin, connexin 30.2 (Cx30.2), and its regulation in the mouse retina. To analyze the expression of Cx30.2, we used a transgenic mouse line in which the coding region of Cx30.2 was replaced by lacZ reporter DNA. We detected the lacZ signal in the nuclei of neurons located in the inner nuclear layer and the ganglion cell layer (GCL). In this study, we focused on the GCL and characterized the morphology of the Cx30.2-expressing cells. Using immunocytochemistry and intracellular dye injections, we found six different types of Cx30.2-expressing ganglion cells: one type of ON-OFF, three types of OFF, and two types of ON ganglion cells; among the latter was the RG A1 type. We show that RG A1 cells were heterologously coupled to numerous displaced amacrine cells. Our results suggest that these gap junction channels may be heterotypic, involving Cx30.2 and a connexin yet unidentified in the mouse retina. Gap junction coupling can be modulated by protein kinases, a process that plays a major role in retinal adaptation. Therefore, we studied the protein kinase-induced modulation of coupling between RG A1 and displaced amacrine cells. Our data provide evidence that coupling of RG A1 cells to displaced amacrine cells is mediated by Cx30.2 and that the extent of this coupling is modulated by protein kinase C.

Connexin channel and its role in diabetic retinopathy

“…In addition to Cx43, it has been reported that a novel retinal connexin called Cx30.2, also known as gap junction protein delta 3 (GJD3), may be involved in facilitating GJIC activity (Muller et al, 2010). Cx30.2 shares 79% identical residues and 84% similar residues with human Cx31.9 protein (Nielsen and Kumar, 2003).…”

“…Cx30.2 shares 79% identical residues and 84% similar residues with human Cx31.9 protein (Nielsen and Kumar, 2003). Furthermore, it is expressed in the heart, vascular smooth muscle, testes, brain, (Nielsen and Kumar, 2003) and retina (Muller et al, 2010). In the mouse retina, Cx30.2 was shown to regulate cell-cell coupling between retinal ganglion cells and amacrine cells (Muller et al, 2010).…”

“…Furthermore, it is expressed in the heart, vascular smooth muscle, testes, brain, (Nielsen and Kumar, 2003) and retina (Muller et al, 2010). In the mouse retina, Cx30.2 was shown to regulate cell-cell coupling between retinal ganglion cells and amacrine cells (Muller et al, 2010). While Cx30.2 was reported to be expressed in the vasculature of different tissues, the effect of HG or the diabetic milieu on Cx30.2 expression and its functional activity was not well known.…”

Characterization of connexin36 gap junctions in the human outer retina

“…Retinal GJs have been shown to play a number of roles in signal processing, including transmission, averaging and synchronization of signals ). In the mammalian retina, Cx36 and Cx45 have been found in both plexiform layers (Gülde-nagel et al 2000;Petrasch-Parwez et al 2004), whereas Cx50 and Cx57 (Massey et al 2003;Hombach et al 2004) are restricted to the outer plexiform layer (OPL) and Cx30.2 is found only in the inner plexiform layer (IPL) (Müller et al 2010). Cx36 and Cx45 have been shown to process rod-mediated signals between AII amacrine and ON cone bipolar cells (BC) and between rod and cone photoreceptors (Feigenspan et al , 2004Güldenagel et al 2001;Mills et al 2001;Deans et al 2002;Lee et al 2003;Völgyi et al 2004;Han and Massey 2005;Maxeiner et al 2005;Lin et al 2005;O'Brien et al 2012), and also serve to correlate ganglion cell signals (Hidaka et al 2004;Schubert et al 2005a, b;Völgyi et al 2005Völgyi et al , 2009Völgyi et al , 2013aPan et al 2010).…”

Cell-cell communication in diabetic retinopathy

“…Interestingly, ganglion cell-amacrine cell coupling is most common for GJIC involving the inner retina (Bloomfield & Volgyi, 2009). Recent research has reported that Cx30.2, a novel gap junction protein in the retinal neurons, facilitates cell-cell coupling between retinal ganglion cell and displaced amacrine cells (Muller, Dedek, Janssen-Bienhold, Meyer, Kreuzberg, Lorenz, Willecke & Weiler, 2010). Although it is unknown whether expression of Cx30.2 is altered in HG condtion in the retinal neuronal cells, it may be plausible since our previous study has shown that HG induces Cx30.2 downregulation in retinal endothelial cells (Manasson et al, 2013).…”