The biogenesis and maturation of nicotinic acetylcholine receptors (nAChRs) in neurons is a complex multi-step process. Receptor maturation is assisted by several chaperones, including RIC-3, which is active in the early stages of receptor assembly and increases the surface expression of mature receptors. Despite its role as a chaperone, elevated RIC-3 levels can be deleterious, as Millet Treinin and colleagues () now report. Using a yeast two-hybrid screen, the authors first identify the protein BATH-42 as an interaction partner of RIC-3. They next show that, in C. elegans, loss of BATH-42 function causes RIC-3 levels to increase; bath-42 loss-of-function worms have reduced nAChR function in vulval muscle. However, the overexpression of bath-2 in adult worms is also deleterious, causing reduced pharyngeal pumping. Notably, this effect is dependent both on RIC-3 and on the CUL-3 ubiquitin ligase complex (with which BATH-42 is known to interact). BATH-42 has a similar domain structure to other CUL-3-binding proteins, which are thought to target specific proteins for ubiquitylation and proteasomal degradation; thus, the authors propose that BATH-42 might regulate RIC-3 levels in a similar way. Their data underscore the importance of regulating chaperone levels in nAChR maturation.
