title: Maintenance of Y receptor dimers in epithelial cells depends on interaction with G-protein heterotrimers.
abstract: Treatment of CHO cells expressing human Y receptors (Y(1), Y(2) or Y4 subtype) with pertussis toxin results in a large decrease in functional receptors, with a preferential loss of heteropentameric assemblies of receptor dimers and G-protein trimers. This occurs in parallel to inactivation of the nucleotide site of Gi α subunits, with a half period of about 4 h. The loss could be mainly due to proteolysis at the level of recycling/perinuclear endosomes, and of receptor completion in the ER, since it is reduced by co-treatment with ammonium chloride, an inhibitor of particulate proteinases. Antagonists do not strongly decrease the heteropentameric fraction. These findings indicate that the upkeep of Y receptor dimers in epithelial cell lines depends on the association of receptor oligomers with functional Gi α subunits. This interaction could use the juxtamembrane helix 8 in the fourth intracellular domain, and could also be supported by the C-terminal helix of the third intracellular loop, as outlined in the companion review (Parker et al., Amino Acids, doi: 10.1007/s00726-010-0616-1 , 2010).
authors.affiliation: Department of Pharmacology, UTHSC Memphis, TN, USA. stevenleonardparker@msn.com
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Estes
authors.forename: Kathleen
authors.initials: K
authors.lastname: McAllen
authors.forename: Michael S
authors.initials: MS
authors.lastname: Parker
authors.forename: Renu
authors.initials: R
authors.lastname: Sah
authors.forename: Trevor
authors.initials: T
authors.lastname: Sweatman
authors.forename: Edwards A
authors.initials: EA
authors.lastname: Park
authors.forename: Ambikaipakan
authors.initials: A
authors.lastname: Balasubramaniam
authors.forename: Floyd R
authors.initials: FR
authors.lastname: Sallee
authors.forename: Mary W
authors.initials: MW
authors.lastname: Walker
authors.forename: Steven L
authors.initials: SL
authors.lastname: Parker
mesh_terms: D000818:Animals; D016466:CHO Cells; D002417:Cattle; D006224:Cricetinae; D003412:Cricetulus; D019281:Dimerization; D004847:Epithelial Cells / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D037342:Pertussis Toxin / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013552:Swine
chemical_list: D017476:Receptors, Neuropeptide Y; D037342:Pertussis Toxin; D020962:Heterotrimeric GTP-Binding Proteins