First identified in yeast and worm and later in other species, the physiological importance of regulators of G-protein signaling (RGS) in mammals was first demonstrated at the turn of the century in mouse retinal photoreceptors, in which RGS9 is needed for timely recovery of rod phototransduction. The role of RGS in vision has been established a synapse away in retinal depolarizing bipolar cells (DBCs), where RGS7 and RGS11 work redundantly and in a complex with Gβ5-S as GAPs for Goα in the metabotropic glutamate receptor 6 pathway at DBC dendritic tips. Much less is known on how RGS protein subserves vision in the rest of the visual system. The research into the roles of RGS proteins in vision holds great potential for many exciting new discoveries.

No abstract

No abstract

RGS6 is a member of the RGS family of proteins that play critical roles in attenuating G protein‐coupled receptor signaling. In addition to a hallmark RGS domain that mediates inactivation of Gi/o subunits, certain RGS6 isoforms possess DEP and GGL domains implicated in their membrane anchoring and binding to Gβ5, respectively. Half of the 36 splice variants of RGS6 we identified in human brain encode DEP domain‐containing long isoforms of RGS6 (RGS6L). In this study, we generated a highly specific antibody against RGS6L isoforms. Using this antibody to evaluate expression of RGS6L in mouse tissues, we identified an immuno‐reactive band corresponding to the predicted molecular weight of RGS6L isoforms in numerous tissues including brain, cerebellum and spinal cord. Moreover, additional unique bands were present in brain, liver and kidney. The size of these other immuno‐reactive proteins could not be accounted for by any known RGS6L transcript. Both the predicted and unique RGS6L immuno‐reactive bands were present in lysates derived from wild‐type but not RGS6 knockout mice, suggesting that the unique bands represent novel isoforms of RGS6L. This is the first evidence that multiple and novel isoforms of RGS6L are present in various mouse tissues. The biological function of the novel isoforms of RGS6L are under investigation. (Supported by NIH GM075033, AHA 0750057Z).