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bioRxiv · 10.1101/2021.05.17.444584

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

Roa, J. N.·Ma, Y.·Mikulski, Z.·Xu, Q.·Ilouz, R.·Taylor, S. S.·Skowronska-Krawczyk, D.
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Abstract

PKA 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 C{beta} 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 C, C{beta}, RII, and RII{beta} subunits. Each subunit presented a distinct localization pattern. C and C{beta} were localized in all tissue layers, while RII and RII{beta} were enriched in the photoreceptor cells in contrast to the cell body and retinal portion of retinal ganglion cells. Only C was observed in photoreceptor outer segments and the cilia transition zone, while C{beta} was localized primarily to mitochondria and was especially prominent in the ellipsoid of the cone cells. In contrast to C, C{beta} also never colocalized with RII or RII{beta}. Using BaseScope technology to track expression of the C{beta} isoforms we find that C{beta}4 and C{beta}4ab are prominently expressed and, therefore, likely code for mitochondrial-C{beta} proteins. Our data indicates that PKA subunits are functionally nonredundant in the retina and suggesting that C{beta} might be important for mitochondrial-associated neurodegenerative diseases previously linked to PKA dysfunction.

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Roa, J. N., Ma, Y., Mikulski, Z., Xu, Q., Ilouz, R., Taylor, S. S., Skowronska-Krawczyk, D.. 2021-05-18. Subcellular localization of PKA catalytic subunits provides a basis for their distinct functions in the retina. https://doi.org/10.1101/2021.05.17.444584

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