Unravelling the physiological role and molecular function of betaine-sensitive nicotinic receptors of Caenorhabditis elegans

TURANI, O.; HERNANDO, G.; BOUZAT, C.

Buenos Aires

Congreso; XXXVI Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias SAN2021; 2021

Sociedad Argentina de Investigación en Neurociencias (SAN)

Betaine is a ubiquitous noncanonical amino acid present in all organisms that functions as an osmolyte and methyl donor. It is also a nematocidal agent, but the underlying molecular mechanism is not known. Betaine is a natural ligand of the nicotinic receptor ACR-23, a ligand-gated non-selective monovalent cation channel. In C. elegans, this receptor maintains the basal levels of locomotion and it is localized in body wall muscle and in mechanosensory neurons. ACR-23 is also a main target of the anthelmintic monepantel, which is a member of the recently identified class of anthelmintics known as the amino-acetonitrile derivatives (AADs). This drug is used to control gastrointestinal nematodes in sheep. It has been postulated that monepantel acts as an agonist and allosteric modulator of ACR-23 in C. elegans. To decipher the activation properties of ACR-23, its modulation by betaine and monepantel, and the underlying mechanisms of these anthelmintic drugs, we carried out behavioural and electrophysiological assays using C. elegans as a model of parasitic nematodes.