Why seemingly all the neuronal membrane-bound receptor are exclusively GPCR or highly homologous to GPCR family?

Question

Nicotinic AchR is known for long to be an ion channel receptor however it has been argued whether it is a GPCR, as well Muscarinic AchR is known to be GPCR. Seemingly many other nerve cell bound receptors like Serotonin receptor, Melatonin receptors, Dopamine receptors, Adrenaline and Nor-adrenaline receptors, known to be G-protein coupled receptor (GPCRs). Although GABA receptors are not directly GPCR by functionality, wikipedia tells a subtype of GABA receptor. is probably GPCR.

So I have basically 2 part in this question:

1. Why GPCR or receptors homologous to GPCR are so common in nerve cells?

2. Are there neuronal receptors which do not have homology with GPCRs?

Answer 1

I think you're confused about proteins that are GPCRs versus having homology. GABA-B is another that is a GPCR (it is not particularly related to GABA-A). These are also called metabotropic receptors.

Ionotropic receptors are from separate families, many from the Cys-loop family (see Sine & Engel, 2006) with a characteristic 5-subunit composition, or the heterotetrameric structure shared among related glutamate receptors (see Dingledine et al 1999).

Your link for nAChR doesn't seem to argue that it is homologous to GPCRs, instead it describes a possible interaction with that channel with g-proteins.

Additionally, none of this is special for neurons: because all modern proteins evolved from previous ones, there is substantial homology within protein families that can often be traced even between vertebrates and bacteria. Within the GPCR family, many different proteins have evolved different sensitivities and different specific g-protein interactions, but the general concept is conserved: something binds outside the cell, causing an internal conformational change that affects a g-protein. The ionotropic receptors are much different.

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Dingledine, R., Borges, K., Bowie, D., & Traynelis, S. F. (1999). The glutamate receptor ion channels. Pharmacological reviews, 51(1), 7-62.

Sine, S. M., & Engel, A. G. (2006). Recent advances in Cys-loop receptor structure and function. Nature, 440(7083), 448.