G protein-coupled receptor kinases and beta arrestins are relocalized and attenuate cyclic 3',5'-adenosine monophosphate response to follicle-stimulating hormone in rat primary Sertoli cells.
The FSH receptor (FSH-R) is a member of the rhodopsin-like subfamily of G protein-coupled receptors that undergoes homologous desensitization upon agonist stimulation. In immortalized cell lines overexpressing the FSH-R, G protein-coupled receptor kinases (GRKs) and beta-arrestins are involved in the phosphorylation, uncoupling, and internalization of this receptor. In an effort to appreciate the physiological relevance of GRK/beta-arrestin actions in natural FSH-R-bearing cells, we used primary rat Sertoli cells as a model. GRK2, -3, -5, -6a, and -6b and beta-arrestins 1 and 2 were expressed in primary rat Sertoli cells. Overexpression of these different GRKs and beta-arrestins in primary rat Sertoli cells significantly attenuated the FSH-induced cAMP response, and FSH rapidly triggered a relocalization of endogenously expressed GRK2, -3, -5, and -6 and beta-arrestins 1 and 2 from the cytosol to the membranes. These results highlight the relationship existing between the GRK/beta-arrestin regulatory system and the FSH-R signaling machinery in a physiological model.
Marion
Sébastien
S
UMR 6073, INRA/CNRS/Université de Tours, Station de Physiologie de la Reproduction et des Comportements, 37380 Nouzilly, France.
Robert
Fabienne
F
Crepieux
Pascale
P
Martinat
Nadine
N
Troispoux
Carine
C
Guillou
Florian
F
Reiter
Eric
E
D000818:Animals; D019390:Arrestins / Q000378:metabolism*; D002469:Cell Separation; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D054768:G-Protein-Coupled Receptor Kinases; D015151:Immunoblotting; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011962:Receptors, FSH / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism*; D014162:Transfection; D000071557:beta-Arrestins
D019390:Arrestins; D011962:Receptors, FSH; D000071557:beta-Arrestins; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP; D017346:Protein Serine-Threonine Kinases; D054768:G-Protein-Coupled Receptor Kinases; C089176:G-protein-coupled receptor kinase 6