Tctex-1 augments G protein-coupled receptor-mediated Gs signaling by activating adenylyl cyclase

Masaki Saito; Ayano Chiba; Takeya Sato; Takahiro Moriya; Jun Sukegawa; Norimichi Nakahata

doi:10.1016/j.jphs.2020.11.011

Tctex-1 augments G protein-coupled receptor-mediated G_s signaling by activating adenylyl cyclase

J Pharmacol Sci. 2021 Jan;145(1):150-154. doi: 10.1016/j.jphs.2020.11.011. Epub 2020 Nov 27.

Authors

Masaki Saito¹, Ayano Chiba², Takeya Sato³, Takahiro Moriya², Jun Sukegawa⁴, Norimichi Nakahata²

Affiliations

¹ Department of Molecular Pharmacology, Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan; Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, 980-8578, Japan. Electronic address: [email protected].
² Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, 980-8578, Japan.
³ Department of Molecular Pharmacology, Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan.
⁴ Department of Molecular Pharmacology, Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan; Department of Human Health and Nutrition, Shokei Gakuin University, Natori, 981-1295, Japan.

PMID: 33357773
DOI: 10.1016/j.jphs.2020.11.011

Abstract

Proteins interacting with G protein-coupled receptors (GPCRs) can modulate signal transduction of these receptors. However, the regulatory mechanisms of the interacting proteins are diverse and largely unknown. We have previously shown that Tctex-1 (or DYNLT1) can interact with the parathyroid hormone receptor (PTHR). In the present study, we investigated the role of Tctex-1 in the PTHR signaling and found that Tctex-1 augmented the PTHR-mediated G_s/adenylyl cyclase (AC) pathway by activating AC regardless of the binding to PTHR. Furthermore, Tctex-1 directly bound to AC type 6. These data demonstrate a novel mechanism underlying GPCR/G_s signaling regulated by Tctex-1.

Keywords: Adenylyl cyclase; Cytoplasmic dynein light chain Tctex-1; Parathyroid hormone receptor.

MeSH terms

3T3 Cells
Adenylyl Cyclases / metabolism*
Animals
Dyneins / metabolism*
Dyneins / physiology*
HEK293 Cells
Humans
Mice
Protein Binding
Receptor, Parathyroid Hormone, Type 1 / metabolism
Receptor, Parathyroid Hormone, Type 1 / physiology
Receptors, G-Protein-Coupled / metabolism*
Signal Transduction / drug effects*
Signal Transduction / genetics*

Substances

DYNLT1 protein, human
Receptor, Parathyroid Hormone, Type 1
Receptors, G-Protein-Coupled
Dyneins
Adenylyl Cyclases
adenylyl cyclase 6