BTB-MATH protein BATH-42 interacts with RIC-3 to regulate maturation of nicotinic acetylcholine receptors

• Published in: Journal of cell science Vol. 122; no. 6; pp. 807 - 812
• Main Authors: Shteingauz, Anna, Cohen, Emiliano, Biala, Yoav, Treinin, Millet
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Limited 15-03-2009
• Subjects: Animals; Caenorhabditis elegans - cytology; Caenorhabditis elegans - drug effects; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - chemistry; Caenorhabditis elegans Proteins - metabolism; Carrier Proteins - chemistry; Carrier Proteins - metabolism; Female; Levamisole - pharmacology; Muscles - cytology; Muscles - drug effects; Muscles - metabolism; Mutation - genetics; Pharynx - cytology; Pharynx - metabolism; Protein Binding; Protein Structure, Tertiary; Protein Transport - drug effects; Receptors, Nicotinic - metabolism; Vulva - cytology; Vulva - drug effects; Vulva - metabolism
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.036343

RIC-3 is a member of a conserved family of proteins that affect nicotinic acetylcholine receptor maturation. In yeast and in vitro, BATH-42, a BTB- and MATH-domain-containing protein, interacts with RIC-3. BATH-42 is also known to interact with the CUL-3 ubiquitin ligase complex. Loss of BATH-42 function leads to increased RIC-3 expression and decreased activity of nicotinic acetylcholine receptors in Caenorhabditis elegans vulva muscles. Increased expression of RIC-3 is deleterious for activity and distribution of nicotinic acetylcholine receptors, and thus the effects of BATH-42 loss of function on RIC-3 expression explain the associated reduction in receptor activity. Overexpression of BATH-42 is also detrimental to nicotinic acetylcholine receptor function, leading to decreased pharyngeal pumping. This effect depends on the C-terminus of RIC-3 and on CUL-3. Thus, our work suggests that BATH-42 targets RIC-3 to degradation via CUL-3-mediated ubiquitylation. This demonstrates the importance of regulation of RIC-3 levels, and identifies a mechanism that protects cells from the deleterious effects of excess RIC-3.