Subcellular localization of PKA catalytic subunits provides a basis for their distinct functions in the retina

Abstract

AbstractPKA signaling is essential for numerous processes but the subcellular localization of specific PKA isoforms has yet to be explored comprehensively in tissues. Expression of the Cβ protein, in particular, has not been mapped previously at the tissue level. In this study we used retina as a window into PKA signaling in the brain and characterized localization of PKA Cα, Cβ, RIIα, and RIIβ subunits. Each subunit presented a distinct localization pattern. Cα and Cβ were localized in all tissue layers, while RIIα and RIIβ were enriched in the photoreceptor cells in contrast to the cell body and retinal portion of retinal ganglion cells. Only Cα was observed in photoreceptor outer segments and the cilia transition zone, while Cβ was localized primarily to mitochondria and was especially prominent in the ellipsoid of the cone cells. In contrast to Cα, Cβ also never colocalized with RIIα or RIIβ. Using BaseScope technology to track expression of the Cβ isoforms we find that Cβ4 and Cβ4ab are prominently expressed and, therefore, likely code for mitochondrial-Cβ proteins. Our data indicates that PKA subunits are functionally nonredundant in the retina and suggesting that Cβ might be important for mitochondrial-associated neurodegenerative diseases previously linked to PKA dysfunction.