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Sci Rep. 2019 Aug 1;9(1):11156. doi: 10.1038/s41598-019-47478-w.

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

Author information

1
BioInvenu Corp., 50 Williams Parkway, Unit A2, East Hanover, NJ, 07936, USA.
2
Laboratory of Chemical Biology & Signal Transduction, The Rockefeller University, 1230 York Avenue, New York, New York, 10065, USA.
3
Department of Neurobiology, Care Sciences and Society, Division for Neurogeriatrics, Center for Alzheimer Research, Karolinska Institutet, 141 57, Huddinge, Sweden.
4
BioInvenu Corp., 50 Williams Parkway, Unit A2, East Hanover, NJ, 07936, USA. haifeng.eishingdrelo@bioinvenu.com.

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 evidence, we propose a working model whereby 14-3-3 serves as a sorting factor to regulate receptor trafficking.

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