Receptor and subunit specific interactions of RIC-3 with nicotinic acetylcholine receptors.
RIC-3 belongs to a conserved family of proteins influencing maturation of nicotinic acetylcholine receptors (nAChRs). RIC-3 homologues were shown to differently affect different nAChRs. Here we show that coexpression with RIC-3 increases the level of surface expression of DEG-3 while slightly reducing the level of surface expression of DES-2, both subunits of the DEG-3/DES-2 nAChRs. Those different effects are a likely explanation for the previously demonstrated effects of RIC-3, an endoplasmic reticulum resident protein, on properties of this receptor. To understand how RIC-3 interacts with different nAChR subunits, we identified and characterized domains and residues enabling this interaction. This analysis shows that conserved residues in the second RIC-3 transmembrane domain are needed for its interactions with two different Caenorhabditis elegans nAChRs, DEG-3/DES-2 and ACR-16. These conserved residues do not, however, function alone; rather, we show that additional domains also enable RIC-3's interactions with these receptors. Interestingly, the relative importance of these residues or of other domains mediating interactions of RIC-3 with nAChRs differs for the two different receptors. Differences in the way that RIC-3, predicted to be an intrinsically disordered protein, interacts with different receptors and receptor subunits suggest that it may adopt different conformations to enable these interactions. Such differences may explain both the effects of RIC-3 on receptor properties and the differences in its effects on different receptors.
Cohen Ben-Ami
Hagit
H
Department of Medical Neurobiology, Institute for Medical Research-Israel-Canada, Hebrew University, Hadassah Medical School, Jerusalem 91120, Israel.
Biala
Yoav
Y
Farah
Hanna
H
Elishevitz
Esty
E
Battat
Emil
E
Treinin
Millet
M
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D011485:Protein Binding; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014981:Xenopus
D029742:Caenorhabditis elegans Proteins; C454142:DEG-3 protein, C elegans; D021122:Protein Subunits; D011978:Receptors, Nicotinic; C099378:acr-16 protein, C elegans; C454141:ric-3 protein, C elegans