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Serotonin 5-[HT.sub.7] receptor slows down the [G.sub.s] protein: a single molecule perspective

Petelak, Ales ; Lambert, Nevin A ; Bondar, Alexey

Molecular biology of the cell, 2023-08, Vol.34 (9), p.1 [Periódico revisado por pares]

American Society for Cell Biology

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  • Título:
    Serotonin 5-[HT.sub.7] receptor slows down the [G.sub.s] protein: a single molecule perspective
  • Autor: Petelak, Ales ; Lambert, Nevin A ; Bondar, Alexey
  • Assuntos: G proteins ; Identification and classification ; Properties ; Receptors ; Serotonin
  • É parte de: Molecular biology of the cell, 2023-08, Vol.34 (9), p.1
  • Descrição: 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 [G.sub.s] 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 [G.sub.s] protein in the plasma membrane. Here, we used single-molecule imaging of the [G.sub.s] protein and 5-H[T.sub.7]R to evaluate [G.sub.s] 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.sub.s]. Expression of the constitutively active mutant 5-HT7R (L173A) is less effective at slowing [G.sub.s] diffusion presumably due to the reduced ability to form long-lasting inactive complexes. An inactive 5-HT7R (N380K) mutant slows down [G.sub.s] to the same extent as the wild-type receptor. We conclude that inactive 5-HT7R profoundly affects [G.sub.s] mobility, which could lead to [G.sub.s] redistribution in the plasma membrane and alter its availability to other G protein-coupled receptors and effectors.
  • Editor: American Society for Cell Biology
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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