Regulation of nicotinic acetylcholine receptors by post-translational modifications

CHRESTIA, JUAN FACUNDO; TURANI, ORNELLA; RODRIGUEZ ARAUJO, NOELIA; HERNANDO, GUILLERMINA; DEL CARMEN ESANDI, MARÍA; BOUZAT, CECILIA

PHARMACOLOGICAL RESEARCH

ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD

Año: 2023

1043-6618

Nicotinic acetylcholine receptors (nAChRs) comprise a family of pentameric ligandgated ion channels widely distributed in the central and peripheric nervous system andin non-neuronal cells. nAChRs are involved in chemical synapses and are key actors invital physiological processes throughout the animal kingdom. They mediate skeletalmuscle contraction, autonomic responses, contribute to cognitive processes, andregulate behaviors. Dysregulation of nAChRs is associated with neurological,neurodegenerative, inflammatory and motor disorders. In spite of the great advances inthe elucidation of nAChR structure and function, our knowledge about the impact ofpost-translational modifications (PTMs) on nAChR functional activity and cholinergicsignaling has lagged behind. PTMs occur at different steps of protein life cycle,modulating in time and space protein folding, localization, function, and protein-proteininteractions, and allow fine-tuned responses to changes in the environment. A largebody of evidence demonstrates that PTMs regulate all levels of nAChR life cycle, withkey roles in receptor expression, membrane stability and function. However, ourknowledge is still limited, restricted to a few PTMs, and many important aspects remainlargely unknown. There is thus a long way to go to decipher the association of aberrantPTMs with disorders of cholinergic signaling and to target PTM regulation for noveltherapeutic interventions. In this review we provide a comprehensive overview of whatis known about how different PTMs regulate nAChR.