14-3-3 signal adaptor and scaffold proteins mediate GPCR trafficking

Scientific Reports
Luwa YuanHaifeng Eishingdrelo

Abstract

Receptor trafficking is pivotal for the temporal and spatial control of GPCR signaling and is regulated by multiple cellular proteins. We provide evidence that GPCRs interact with 14-3-3 signal adaptor/scaffold proteins and that this interaction regulates receptor trafficking in two ways. We found GPCR/14-3-3 interaction signals can be agonist-induced or agonist-inhibited. Some GPCRs associate with 14-3-3 proteins at the cell membrane and agonist treatments result in disrupted GPCR/14-3-3 interaction signals. The diminished GPCR/14-3-3 interaction signals are temporally correlated with increased GPCR/β-arrestin interaction signals in response to agonist treatment. Other GPCRs showed agonist-induced GPCR/14-3-3 interaction signal increases that occur later than agonist-induced GPCR/β-arrestin interaction signals, indicating that GPCR/14-3-3 interaction occurred after receptor endocytosis. These two types of GPCR/14-3-3 interaction patterns correlate with different receptor trafficking patterns. In addition, the bioinformatic analysis predicts that approximately 90% of GPCRs contain at least one putative 14-3-3 binding motif, suggesting GPCR/14-3-3 association could be a general phenomenon. Based on these results and collective e...Continue Reading

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Citations

Feb 16, 2021·Frontiers in Pharmacology·Emma T van der WesthuizenArthur Christopoulos
Sep 25, 2021·Journal of Neuroscience Research·Jade DegrandmaisonLouis Gendron

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Methods Mentioned

BETA
ubiquitination
LinkLight
PCR
environmental stresses
GTPase
co-immunoprecipitation
pharmacotherapy
transfection

Software Mentioned

14
1433pred
GraphPad
Prism
GPCRdb
LinkLight
3pred
3pred tool

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