Non-traditional roles of G protein-coupled receptors in basic cell biology

Abstract

G protein-coupled receptors (GPCR) are key signaling proteins that regulate how cells interact with their environments. Traditional signaling cascades involving GPCRs have been well described and are well established and very important clinical targets. With the development of more recent technologies, hints about the involvement of GPCRs in fundamental cell biological processes are beginning to emerge. In this review, we give a basic introduction to GPCR signaling and highlight some less well described roles of GPCRs, including in cell division and membrane trafficking, which may occur through canonical and non-canonical signaling pathways.

The primary cilium as a cellular receiver: organizing ciliary GPCR signaling

“…The type of downstream signaling activated depends in part on the specific G α that is coupled to the GPCR (G αs , G αi/o , G αq , and G α12/13 ). Additionally, GPCRs can signal independently of G-proteins and there is growing literature on GPCR-independent G-protein signaling [9]. GPCR signaling components that to date have been identified as being localized to the primary cilium are summarized in Table 1B.…”

cAMP signaling in subcellular compartments

“…The canonical view is that internalization of GPCRs is part of the receptor desensitization process and involves receptor phosphorylation by G protein-coupled receptor kinases, recruitment of beta-arrestin and consequent GPCR internalization (Kamal et al, 2012). Once internalized, GPCRs can be re-exposed, in their inactive state, at the plasma membrane or, alternatively, can be targeted for degradation (Zhang and Eggert, 2013). Recent studies, however, have challenged this dogma by showing that internalized GPCRs maintain their ability to trigger cAMP production (Calebiro et al, 2009; Ferrandon et al, 2009; Irannejad et al, 2013).…”

Application of plasma lipidomics in studying the response of patients with essential hypertension to antihypertensive drug therapy

“…lipidomics) at the molecular level and have aided in the characterisation of biomarkers of health/disease and drug/nutritional effect. [23][24][25][26][27] Recently, several hypertensionrelated studies have been reported in the literature. 15,[28][29][30][31] However, these studies focused only on investigating the differentiation of target compound/metabolites between hypertensive and normotensive subjects; none of the studies reported the effects of antihypertensive agents by comparing the lipid metabolism in hypertensive subjects before and after treatment.…”