Identification of novel stiffness sensor GPCRs and functional analysis in muscular tissues

• Published in: Proceedings for Annual Meeting of The Japanese Pharmacological Society Vol. 94; p. 2-S16-2
• Main Authors: Nishimura, Akiyuki, Sakata, Kosuke, Tanaka, Tomohiro, Nishiyama, Kazuhiro, Kato, Yuri, Nishida, Motohiro
• Format: Journal Article
• Language: Japanese; English
• Published: Japanese Pharmacological Society 2021
• ISSN: 2435-4953; 2435-4953
• DOI: 10.1254/jpssuppl.94.0_2-S16-2

The living tissues have an optimized stiffness to perform their proper functions. It has been reported that stiffness of the extracellular environment plays major roles in determining cell fate in various cell types. To understand how cells recognize and respond to non-uniform stiffness of tissue, integrated analysis and characteristics of a series of stiffness sensing receptors are required. However, only a few stiffness responsible receptors have been identified, and it is still mostly unclear how cells recognize non-uniform stiffness through coordination of stiffness sensing receptors. G protein-coupled receptors (GPCRs) are a major class of transmembrane receptors which are responsible to various types of extracellular ligands. Recently, we found that several GPCRs can be activated by the differences of extracellular substrate stiffness. Using GPCR expression plasmid library, we identified seven GPCRs that are activated by soft substrate such as PDMS. These receptor show permanent calcium oscillation under soft substrate without receptor desensitization. In this talk, we introduce activation properties of stiffness sensing GPCRs and discuss their physiological and pathophysiological meaning.