Pestic Biochem Physiol 2023 May 01;192:105384. doi: 10.1016/j.pestbp.2023.105384.

A consensus phosphoserine within the large cytoplasmic loop of insect nAChR α8 subunits modulated interaction between 14-3-3ε and nAChRs to regulate neonicotinoid efficacy.

???displayArticle.abstract???
Neonicotinoids are insect-selective nicotinic acetylcholine receptors (nAChRs) agonists that are used extensively for plant protection and animal health care. Some chaperone proteins, such as 14-3-3 proteins, importantly modulate nAChRs to display the physiological and pharmacological properties. Here we found that there is a 14-3-3 binding motif RSPSTH within the cytoplasmic loop of most insect α8 subunits. In the motif, a potential phosphorylated serine residue, serine 337, was a putative protein kinase A (PKA) substrate. Using Locusta migratoria α8 subunit as a representative, here we demonstrated that Loc14-3-3ε interacted with the unique phosphoserine (α8S337) of Locα8 subunit to regulate agonist efficacy on hybrid Locα8/β2 nAChRs in Xenopus oocytes. Co-expression of Loc14-3-3ε caused a dramatic rise of maximal inward currents (Imax) of Locα8/β2 for acetylcholine and imidacloprid to 2.9-fold and 3.1-fold of that of Locα8/β2 alone. The S337A substitution of Locα8 reduced the Imax rise when Locα8S337A/β2 and Loc14-3-3ε were co-expressed. The increased agonist currents by exogenous Loc14-3-3ε on Locα8/β2 could be almost abolished by either PKA inhibitor KT5720 or 14-3-3 inhibitor difopein. The findings revealed that serine 337 within motif RSPSTH was important for the interaction between insect nAChRs and 14-3-3ε, and inhibiting the interaction would change the pharmacological property of insect nAChRs to agonist such as neonicotinoids which may provide insights to develop new targets for insecticide design.

???displayArticle.pubmedLink??? 37105614
???displayArticle.link??? Pestic Biochem Physiol