Spatiotemporal dimensions of signaling
Optical mapping reveals spatiotemporal GPCR signaling at the nanoscale
The viral-encoded US28 receptor contributing to glioblastoma development constitutively activates Gq from early endosomes
Investigating GPCR signalling in adipocytes
It is now established that metabolites not only act as building blocks for biosynthetic pathways, but are also bona fide signaling molecules. The signaling functions of metabolites are largely dependent on their intra- and extracellular concentrations as well as their subcellular compartmentalisation. Notably, deregulation of metabolite signaling is implicated in numerous human diseases, including that of diabetes and obesity. In response, metabolite-sensing GPCRs have emerged as attractive therapeutic targets. Therefore, better understanding the physiological role as well as the underlying mechanism of metabolite sensing GPCRs is of great interest.
Here, we describe the use of mini-G protein (mG) probes (Wan et al., 2018), bioluminescence resonance energy transfer (BRET), and advanced imaging methods, to provide evidence that the free fatty acid receptor 4 (FFAR4)/GPR120, a GPCR responsive to medium and long chain fatty acids and known to be highly expressed in adipocytes, can signal from intracellular compartments in a Gαi/o dependent manner and FFAR4 compartmentalization is essential for its activation after the induction of lipolysis (Husted et al., 2020).
WAN, Q., OKASHAH, N., INOUE, A., NEHME, R., CARPENTER, B., TATE, C. G. & LAMBERT, N. A. 2018. Mini G protein probes for active G protein-coupled receptors (GPCRs) in live cells. J Biol Chem, 293, 7466-7473.
HUSTED, A. S., TRAUELSEN, M., RUDENKO, O., HJORTH, S. A. & SCHWARTZ, T. W. 2017. GPCR-Mediated Signaling of Metabolites. Cell Metab, 25, 777-796.