Talk:G protein-coupled receptor

This is a nice review that covers the essence of a very large and diverse topic in a succinct way. I have two subtopics that I think are of interest to the Neuroscience community that could be added to the review without significantly lengthening it. I realize that with a topic this large, there are many subtopics that can’t be reasonably covered in an article of this size.

1. In addition to GalphaS, there is good evidence that GalphaOLF (GNAL, Golf) couples to dopamine D1 and adenosine A2A receptors in striatum to stimulate adenylate cyclase (e.g., Zhuang et al. G(olf)alpha mediates dopamine D1 receptor signaling. J Neurosci 20:RC91, 2000; Corvol et al. Galpha(olf) is necessary for coupling D1 and A2a receptors to adenylyl cyclase in the striatum. J Neurochem 76:1585-8, 2001). Given the proposed importance of these pathways in various clinical conditions, especially addictive behaviors, I feel this pathway could be added to GalphaS coupling section.

2. In addition to GPCR homo- and hetero-dimerization, another emerging topic is the idea of GPCR signaling to effectors without utilizing heterotrimeric G-proteins. At this point, the field is not very well developed and evidence for such pathways is sparse although slowly accumulating. A recent example, relevant to the Neuroscience community, would be activation of the ion channel NALCN via substance P/neurotensin and mAChR receptors (Lu et al. Peptide neurotransmitters activate a cation channel complex of NALCN and UNC-80. Nature 457:741-4, 2009; Swayne et al. The NALCN ion channel is activated by M3 muscarinic receptors in a pancreatic beta-cell line. EMBO reports 10:873-80, 2009). ). There are other examples of this phenomenon in the literature (reviewed by Sun et al. When a G protein-coupled receptor does not couple to a G protein. Mol Biosyst 3:849-54, 2007).

Reviewer A:

This is a very nice short review of GPCRs and how they are involved in signaling primarily from the point of view of a neurobiologist. It covers the most important aspects of GPCRs and G proteins, is carefully written and avoids any unnecessary speculations.

I have only one specific suggestion: After describing the different receptor families it would be nice to briefly touch the evolutionary aspect of GPCR developement: The ligand selectivity appeared before the generation of G protein selectivity. Therefore each receptor family independently spread into subtypes that were able to distinguish the G protein families.