The puzzling uniqueness of the heterotrimeric G15 protein and its potential beyond hematopoiesis.
Heterotrimeric G proteins transduce the signals of the largest family of membrane receptors (G protein-coupled receptors, GPCRs) hence triggering the activation of a wide variety of physiological responses. G15 is a G protein characterized by a number of functional peculiarities that make its signaling exceptional: 1) it can couple a variety of Gs-, Gi/o-, and Gq-linked receptors to phospholipase C activation; 2) relatively to other G proteins, it is poorly affected by beta-arrestin-dependent desensitization, the general mechanism that regulates GPCR function and 3) at the protein level, its expression is only detected in highly specific cell types (hematopoietic and epithelial cells). G15 alpha-subunit displays unique structural and biochemical properties, and is phylogenetically the most recent and divergent component of the Galphaq/11 subfamily. All these aspects shed a mysterious light on G15 biological role, which remains substantially elusive. Thus, far, G15 signaling has been analyzed in the context of hematopoiesis. Here, we highlight observations supporting the view that G15 functions may extend further beyond the immune system. In addition, we describe puzzling aspects of G15 signaling that offer a novel perspective in the understanding of its physiological role.
Department of Experimental Medicine, University of Milano-Bicocca, Monza 20052, Italy.
Flavia
F
Giannone
Giorgio
G
Malpeli
Veronica
V
Lisi
Silvia
S
Grasso
Priyanka
P
Shukla
Dunia
D
Ramarli
Silvia
S
Sartoris
Vladia
V
Monsurró
Mauro
M
Krampera
Eliana
E
Amato
Giuseppe
G
Tridente
Marco
M
Colombatti
Marco
M
Parenti
Giulio
G
Innamorati
D000818:Animals; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics / Q000502:physiology*; D006410:Hematopoiesis; D006801:Humans; D010802:Phylogeny; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction
D044385:GTP-Binding Protein alpha Subunits; D043562:Receptors, G-Protein-Coupled