AUTHOR=Guo Paipai , Tai Yu , Wang Manman , Sun Hanfei , Zhang Lingling , Wei Wei , Xiang Yang K. , Wang Qingtong 

TITLE=Gα12 and Gα13: Versatility in Physiology and Pathology

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.809425

DOI=10.3389/fcell.2022.809425

ISSN=2296-634X

ABSTRACT=<p>G protein-coupled receptors (GPCRs), as the largest family of receptors in the human body, are involved in the pathological mechanisms of many diseases. Heterotrimeric G proteins represent the main molecular switch and receive cell surface signals from activated GPCRs. Growing evidence suggests that Gα<sub>12</sub> subfamily (Gα<sub>12/13</sub>)-mediated signaling plays a crucial role in cellular function and various pathological processes. The current research on the physiological and pathological function of Gα<sub>12/13</sub> is constantly expanding, Changes in the expression levels of Gα<sub>12/13</sub> have been found in a wide range of human diseases. However, the mechanistic research on Gα<sub>12/13</sub> is scattered. This review briefly describes the structural sequences of the Gα<sub>12/13</sub> isoforms and introduces the coupling of GPCRs and non-GPCRs to Gα<sub>12/13</sub>. The effects of Gα<sub>12/13</sub> on RhoA and other signaling pathways and their roles in cell proliferation, migration, and immune cell function, are discussed. Finally, we focus on the pathological impacts of Gα<sub>12/13</sub> in cancer, inflammation, metabolic diseases, fibrotic diseases, and circulatory disorders are brought to focus.</p>