Serotonin 5-HT7 receptor slows down the G(s) protein: a single molecule perspective

0574910 - MBÚ 2024 RIV US eng J - Journal Article
Petelák, Aleš - Lambert, N. A. - Bondar, Alexey
Serotonin 5-HT7 receptor slows down the G(s) protein: a single molecule perspective.
Molecular Biology of the Cell. Roč. 34, č. 9 (2023), br14. ISSN 1059-1524. E-ISSN 1939-4586
R&D Projects: GA ČR(CZ) GJ20-09628Y; GA MŠMT(CZ) LTC20074
Institutional support: RVO:61388971 ; RVO:60077344
Keywords : 5-hydroxytryptamine * Gs mobility * nervous system * plasma membrane
OECD category: Microbiology; Biochemistry and molecular biology (BC-A)
Impact factor: 3.3, year: 2022
Method of publishing: Open access
https://www.molbiolcell.org/doi/10.1091/mbc.E23-03-0117

The 5-hydroxytryptamine (serotonin) receptor type 7 (5-HT7R) is a G protein-coupled receptor present primarily in the nervous system and gastrointestinal tract, where it regulates mood, cognition, digestion, and vasoconstriction. 5-HT7R has previously been shown to bind to its cognate stimulatory Gs protein in the inactive state. This phenomenon, termed ´inverse coupling,´ is thought to counteract the atypically high intrinsic activity of 5-HT7R. However, it is not clear how active and inactive 5-HT7 receptors affect the mobility of the Gs protein in the plasma membrane. Here, we used single-molecule imaging of the Gs protein and 5-HT7R to evaluate Gs mobility in the membrane in the presence of 5-HT7R and its mutants. We show that expression of 5-HT7R dramatically reduces the diffusion rate of G(s). Expression of the constitutively active mutant 5-HT7R (L173A) is less effective at slowing Gs diffusion presumably due to the reduced ability to form long-lasting inactive complexes. An inactive 5-HT7R (N380K) mutant slows down Gs to the same extent as the wild-type receptor. We conclude that inactive 5-HT7R profoundly affects Gs mobility, which could lead to Gs redistribution in the plasma membrane and alter its availability to other G protein-coupled receptors and effectors.
Permanent Link: https://hdl.handle.net/11104/0344842