ePoster

Modulation of AKT and ribosomal S6 protein phosphorylation by dopamine receptors and cyclic AMP in the developing retina

Roberto Paes-de-Carvalho, Lohan Ximenes, Arthur Barbieri
FENS Forum 2024(2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Roberto Paes-de-Carvalho, Lohan Ximenes, Arthur Barbieri

Abstract

Dopamine-dependent cyclic AMP accumulation occurs via activation of D1-like receptors since early development of the chicken retina. Cyclic AMP is an ubiquitous second messenger that regulates several physiological processes including neuronal survival and differentiation. The mTOR pathway is a crucial pathway linking cellular metabolism to protein synthesis. The mTORC1 and 2 signaling complexes are composed of mTOR and distinct proteins, and while mTORC1 is regulated by AKT, mTORC2 is upstream of this enzyme and regulates phosphorylation of its serine 473 residue. Ribosomal protein S6 (RpS6) is phosphorylated by S6K1, both considered markers of mTORC1 activity. Here we studied the pathways regulating AKT and RpS6 phosphorylation and its modulation by cyclic AMP and dopamine receptors in the developing retina. Retinas from 10-day-old chicken embryos (E10), an early stage of development, and E16, a more developed stage, were incubated with the adenylyl cyclase stimulator forskolin or dopamine. Retinas were lysed and analysed by western blotting using antibodies against phosho-RpS6 (ser 240/244) or phospho-AKT (ser 473). Interestingly, forskolin or dopamine produce a strong inhibition of AKT phosphorylation but an increase of RpS6 phosphorylation in E10 or E16 retinas (see figure). The effect of dopamine is blocked by SCH23390, a D1 receptor antagonist, or SQ22536, an adenylyl cyclase inhibitor. The effects of forskolin or dopamine on RpS6, but not on AKT phosphorylation, are blocked by ESI 09, an EPAC inhibitor. Our results indicate that cyclic AMP and its regulation by dopamine D1 receptors controls RpS6 and AKT phosphorylation through different mechanims during retinal development.

Unique ID: fens-24/modulation-ribosomal-protein-phosphorylation-a5d6d895