Regulation of nicotinic acetylcholine receptors by post-translational modifications

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

PHARMACOLOGICAL RESEARCH

ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD

Año: 2023

1043-6618

Nicotinic acetylcholine receptors (nAChRs) comprise a family of pentameric ligand-gated ion channels widelydistributed in the central and peripheric nervous system and in non-neuronal cells. nAChRs are involved inchemical synapses and are key actors in vital physiological processes throughout the animal kingdom. Theymediate skeletal muscle contraction, autonomic responses, contribute to cognitive processes, and regulate behaviors. Dysregulation of nAChRs is associated with neurological, neurodegenerative, inflammatory and motordisorders. In spite of the great advances in the elucidation of nAChR structure and function, our knowledge aboutthe impact of post-translational modifications (PTMs) on nAChR functional activity and cholinergic signaling haslagged behind. PTMs occur at different steps of protein life cycle, modulating in time and space protein folding,localization, function, and protein-protein interactions, and allow fine-tuned responses to changes in the environment. A large body of evidence demonstrates that PTMs regulate all levels of nAChR life cycle, with key rolesin receptor expression, membrane stability and function. However, our knowledge is still limited, restricted to afew PTMs, and many important aspects remain largely unknown. There is thus a long way to go to decipher theassociation of aberrant PTMs with disorders of cholinergic signaling and to target PTM regulation for noveltherapeutic interventions. In this review we provide a comprehensive overview of what is known about howdifferent PTMs regulate nAChR