Muscarinic acetylcholine receptor-interacting proteins (mAChRIPs): targeting the receptorsome (original) (raw)

Muscarinic acetylcholine receptors comprise a large family of G protein-coupled receptors that are involved in the regulation of many important functions of the central and peripheral nervous system. To achieve such a large range of physiological effects, these receptors interact, in addition to the canonical heterotrimeric G proteins, with a large array of accessory proteins including scaffold molecules, ion channels and enzymes which operate as molecular transducers of muscarinic function. Interestingly, as demonstrated for others G protein-coupled receptors this type of receptors are also able to oligomerize, a fact that has been shown to play a critical role in their subcellular distribution, trafficking, and finetuning modulation of cholinergic signalling. On the other hand, the specificity of these receptor interactions may be largely determined by the occurrence of precise protein-interacting motifs, posttranslational modifications, and the differential tissue distribution and stoichiometry of the receptor-interacting proteins. Thus, the exhaustive cataloguing and documentation of muscarinic acetylcholine receptors interacting proteins and the grasp of their specific function will explain some key physiological differences in muscarinic-mediated cholinergic transmission. Overall, a better comprehension of the muscarinic receptor interactome will have by sure a great impact on the cholinergic pharmacology and thus providing previously unrealized opportunities to achieve greater specificity in muscarinic-related drug discovery and diagnostic.