The BTB-MATH protein BATH-42 interacts with RIC-3 to regulate maturation of nicotinic acetylcholine receptors.
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.
Shteingauz
Anna
A
Department of Physiology, Hebrew University, Hadassah Medical School, Jerusalem, 91120, Israel.
Cohen
Emiliano
E
Biala
Yoav
Y
Treinin
Millet
M
D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D005260:Female; D007978:Levamisole / Q000494:pharmacology; D009132:Muscles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010614:Pharynx / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014844:Vulva / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
C541237:BATH-42 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D011978:Receptors, Nicotinic; C454141:ric-3 protein, C elegans; D007978:Levamisole