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14-3-3 signal adaptor and scaffold proteins mediate GPCR trafficking
Luwa Yuan1, Shahar Barbash2, Sathapana Kongsamut1
1BioInvenu Corp., 50 Williams Parkway, Unit A2, East Hanover, NJ, 07936, USA.
Scientific Reports
|August 3, 2019
Summary
G protein-coupled receptors (GPCRs) interact with 14-3-3 proteins, regulating their trafficking. This interaction can be agonist-induced or inhibited, influencing receptor localization and signaling pathways.
Area of Science:
- Cellular Biology
- Molecular Biology
- Biochemistry
Background:
- Receptor trafficking is crucial for controlling G protein-coupled receptor (GPCR) signaling.
- GPCRs are regulated by various cellular proteins, including signal adaptors.
Purpose of the Study:
- To investigate the interaction between GPCRs and 14-3-3 proteins.
- To elucidate the role of this interaction in regulating GPCR trafficking.
Main Methods:
- Studied GPCR and 14-3-3 protein interactions.
- Analyzed agonist-induced and inhibited interaction signals.
- Correlated interaction patterns with receptor trafficking.
- Performed bioinformatic analysis for 14-3-3 binding motifs in GPCRs.
Main Results:
- GPCR/14-3-3 interactions are modulated by agonists, either decreasing or increasing.
- Decreased GPCR/14-3-3 interaction correlates with increased GPCR/β-arrestin interaction at the membrane.
- Increased GPCR/14-3-3 interaction occurs post-endocytosis for some receptors.
- Bioinformatic analysis suggests ~90% of GPCRs may bind 14-3-3 proteins.
Conclusions:
- GPCR/14-3-3 interactions play a dual role in regulating receptor trafficking.
- These interactions are linked to distinct receptor trafficking patterns.
- 14-3-3 proteins likely act as sorting factors in GPCR trafficking.
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