Maintenance of Y receptor dimers in epithelial cells depends on interaction with G-protein heterotrimers.
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).
Estes
Anne-Marie
AM
Department of Pharmacology, UTHSC Memphis, TN, USA. stevenleonardparker@msn.com
McAllen
Kathleen
K
Parker
Michael S
MS
Sah
Renu
R
Sweatman
Trevor
T
Park
Edwards A
EA
Balasubramaniam
Ambikaipakan
A
Sallee
Floyd R
FR
Walker
Mary W
MW
Parker
Steven L
SL
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
D017476:Receptors, Neuropeptide Y; D037342:Pertussis Toxin; D020962:Heterotrimeric GTP-Binding Proteins