The Subcellular Dynamics of the Gs-Linked Receptor GPR3 Contribute to the Local Activation of PKA in Cerebellar Granular Neurons

PloS One
Tatsuhiro MiyagiNorio Sakai

Abstract

G-protein-coupled receptor (GPR) 3 is a member of the GPR family that constitutively activates adenylate cyclase. We have reported that the expression of GPR3 in cerebellar granular neurons (CGNs) contributes to neurite outgrowth and modulates neuronal proliferation and survival. To further identify its role, we have analyzed the precise distribution and local functions of GPR3 in neurons. The fluorescently tagged GPR3 protein was distributed in the plasma membrane, the Golgi body, and the endosomes. In addition, we have revealed that the plasma membrane expression of GPR3 functionally up-regulated the levels of PKA, as measured by a PKA FRET indicator. Next, we asked if the PKA activity was modulated by the expression of GPR3 in CGNs. PKA activity was highly modulated at the neurite tips compared to the soma. In addition, the PKA activity at the neurite tips was up-regulated when GPR3 was transfected into the cells. However, local PKA activity was decreased when endogenous GPR3 was suppressed by a GPR3 siRNA. Finally, we determined the local dynamics of GPR3 in CGNs using time-lapse analysis. Surprisingly, the fluorescent GPR3 puncta were transported along the neurite in both directions over time. In addition, the anterograde ...Continue Reading

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Citations

Feb 3, 2018·Drug Metabolism Reviews·Paula MoralesPatricia H Reggio
Jul 1, 2020·Genes·Lyndsay R Watkins, Cesare Orlandi
Jul 25, 2018·Scientific Reports·Stefano CapaldiMario Buffelli
Aug 14, 2018·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Shigeru Tanaka
Feb 17, 2021·Molecular Psychiatry·Ioannis MantasPer Svenningsson

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Methods Mentioned

BETA
transfection
PCR
FRET
confocal microscopy
Fluorescence

Software Mentioned

Deltagen
MetaMorph

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