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

Lugar: Amsterdam; Año: 2023

1043-6618

Nicotinic acetylcholinereceptors (nAChRs) comprise a family of pentameric ligand-gated ionchannels widely distributed in the central and peripheric nervous system and in non-neuronal cells. nAChRs are involved in chemicalsynapses and are key actors in vital physiological processesthroughout the animal kingdom. They mediate skeletal muscle contraction, autonomic responses, contribute tocognitive processes, and regulate behaviors.Dysregulation of nAChRs is associated with neurological, neurodegenerative, inflammatory and motor disorders. In spiteof the great advances in the elucidation of nAChRstructure and function, our knowledge about the impact of post-translational modifications (PTMs) on nAChR functionalactivity and cholinergic signaling has lagged behind.PTMs occur at different steps of protein life cycle, modulating in time and space protein folding, localization,function, and protein-protein interactions, and allowfine-tuned responses to changes in the environment. A large body of evidence demonstrates that PTMs regulate all levelsof nAChR life cycle, with key roles in receptor expression,membrane stability and function. However, our knowledgeis still limited, restricted to a few PTMs, and many important aspects remain largely unknown. There is thus a long way to go to decipherthe association of aberrant PTMs with disorders ofcholinergic signaling and to target PTM regulation for novel therapeutic interventions. In this review we provide acomprehensive overview of what is known about how differentPTMs regulate nAChR.