Abstract
Electrical coupling via gap junctions is an abundant phenomenon in the mammalian retina and occurs in all major cell types. Gap junction channels are assembled from different connexin subunits, and the connexin composition of the channel confers specific properties to the electrical synapse. In the mouse retina, gap junctions were demonstrated between intrinsically photosensitive ganglion cells and displaced amacrine cells but the underlying connexin remained undetermined. In the primary rod pathway, gap junctions play a crucial role, coupling AII amacrine cells among each other and to ON cone bipolar cells. Although it has long been known that connexin36 and connexin45 are necessary for the proper functioning of this most sensitive rod pathway, differences between homocellular AII/AII gap junctions and AII/ON bipolar cell gap junctions suggested the presence of an additional connexin in AII amacrine cells. Here, we used a connexin30.2-lacZ mouse line to study the expression of connexin30.2 in the retina. We show that connexin30.2 is expressed in intrinsically photosensitive ganglion cells and AII amacrine cells. Moreover, we tested whether connexin30.2 and connexin36—both expressed in AII amacrine cells—are able to interact with each other and are deposited in the same gap junctional plaques. Using newly generated anti-connexin30.2 antibodies, we show in HeLa cells that both connexins are indeed able to interact and may form heteromeric channels: both connexins were co-immunoprecipitated from transiently transfected HeLa cells and connexin30.2 gap junction plaques became significantly larger when co-expressed with connexin36. These data suggest that connexin36 is able to form heteromeric gap junctions with another connexin. We hypothesize that co-expression of connexin30.2 and connexin36 may endow AII amacrine cells with the means to differentially regulate its electrical coupling to different synaptic partners.
Highlights
In the central nervous system, electrical synapses constitute a fast means of intercellular communication, directly transmitting electrical signals from one adjacent cell to another
Five different connexin isoforms have been identified in neurons: (1) Cx36, expressed in cone photoreceptors (Feigenspan et al, 2004; Bolte et al, 2015), bipolars (Deans et al, 2002; Han and Massey, 2005), amacrine cells (Feigenspan et al, 2001; Brüggen et al, 2015) and many types of ganglion cells (Pan et al, 2010); (2) Cx45, expressed in bipolar (Maxeiner et al, 2005; Dedek et al, 2006; Hilgen et al, 2011), amacrine (Dedek et al, 2009) and bistratified ganglion cells (Schubert et al, 2005); (3,4) Cx50 and Cx57, both expressed in horizontal cells (Hombach et al, 2004; Dorgau et al, 2015); and (5) Cx30.2, expressed in six types of ganglion cells and an as yet uncharacterized amacrine cell type (Müller et al, 2010a)
We show that Cx30.2 is expressed in intrinsically photosensitive retinal ganglion cells (ipRGC) and AII amacrine cells of the mouse retina
Summary
In the central nervous system, electrical synapses (gap junctions) constitute a fast means of intercellular communication, directly transmitting electrical signals from one adjacent cell to another. Gap junction channels consist of two hemichannels (connexons), each of which is provided by one cell and formed by a hexamer of connexin (Cx) subunits (Kumar and Gilula, 1996). 20 connexin isoforms have been identified (Söhl and Willecke, 2003). Some of these isoforms are able to associate to form heteromeric connexons or heterotypic gap junction channels, with hemi-channel composition differing between the two adjacent cells. As the connexin composition determines the permeability and gating properties of a gap junction channel, a great variety in physiological properties is achieved, which is further enhanced by posttranslational modifications, such as phosphorylation (Söhl and Willecke, 2003). Five different connexin isoforms have been identified in neurons: (1) Cx36, expressed in cone photoreceptors (Feigenspan et al, 2004; Bolte et al, 2015), bipolars (Deans et al, 2002; Han and Massey, 2005), amacrine cells (Feigenspan et al, 2001; Brüggen et al, 2015) and many types of ganglion cells (Pan et al, 2010); (2) Cx45, expressed in bipolar (Maxeiner et al, 2005; Dedek et al, 2006; Hilgen et al, 2011), amacrine (Dedek et al, 2009) and bistratified ganglion cells (Schubert et al, 2005); (3,4) Cx50 and Cx57, both expressed in horizontal cells (Hombach et al, 2004; Dorgau et al, 2015); and (5) Cx30.2, expressed in six types of ganglion cells and an as yet uncharacterized amacrine cell type (Müller et al, 2010a)
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