Alteration of cell membrane proteoglycans impairs FSH receptor/Gs coupling and ERK activation through PP2A-dependent mechanisms in immature rat Sertoli cells

• Published in: Biochimica et biophysica acta Vol. 1830; no. 6; pp. 3466 - 3475
• Main Authors: Levallet, Guénaëlle, Bonnamy, Pierre-Jacques, Levallet, Jérôme
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2013; Elsevier
• Subjects: Animals; cAMP-dependent protein kinase; cell membranes; cell proliferation; Cells, Cultured; cholera; cyclic AMP; Cyclic AMP - metabolism; Cyclic AMP-Dependent Protein Kinases - metabolism; follicle-stimulating hormone; follicle-stimulating hormone receptors; FSH signaling; Heparan sulfate proteoglycan; Life Sciences; Male; MAP Kinase Signaling System - physiology; mitogen-activated protein kinase; Mitogen-Activated Protein Kinase 3 - metabolism; okadaic acid; phosphorylation; Protein Phosphatase 2 - metabolism; Protein phosphatase 2A; proteoglycans; Rats; Rats, Sprague-Dawley; Receptors, FSH - agonists; Receptors, FSH - metabolism; Second Messenger Systems - physiology; Sertoli cell; Sertoli cells; Sertoli Cells - metabolism; Sheep; sodium chlorate; Syndecan-1; Syndecan-1 - metabolism; Sertoli cell; HSPG; PP2A; MAPK; SC; OA; FSH signaling; FBS; Syndecan-1; PGs; ERK; Heparan sulfate proteoglycan; Protein phosphatase 2A; INTACT-CELLS; PROTEIN PHOSPHATASE 2A; EPITHELIAL-CELLS; BETA-ARRESTINS; AGE-RELATED-CHANGES; BINDING PROTEINS; FOLLICLE-STIMULATING-HORMONE; HEPARAN-SULFATE PROTEOGLYCANS; SIGNAL-REGULATED KINASE; ESTRADIOL PRODUCTION
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2013.02.027

During the pre-pubertal life, the cessation of Sertoli cell proliferation and the onset of differentiation are associated with a shift in the FSH-mediated signaling leading to inhibition of the ERK-mitogenic pathway and to a concomitant sensitization of cAMP/PKA pathway. To highlight the role of cell proteoglycans (PGs) in the shift of FSH signaling, both FSH-induced cAMP production and ERK1/2 inactivation were studied in untreated and sodium chlorate PG-depleted cultured Sertoli cells from 20day-old rats. Depletion of cell membrane PGs by sodium chlorate reduced FSH-, but not cholera toxin-stimulated cAMP production as well as basal ERK phosphorylation through an okadaic acid (OA)-sensitive mechanism. Involvement of PP2A was further substantiated by a marked decrease in membrane- associated PP2A activity under SC conditions and by the OA-induced restoration of PKA-dependent ERK inactivation in SC-treated cells. In 20-day-old rat Sertoli cells, transmembrane cell PGs, through tethering/activation of PP2A activity exerts regulatory control on both FSH receptor/Gs coupling and ERK phosphorylation. Besides their antiproliferative roles, cell PGs such as syndecan-1, could be involved in the increase in cAMP response to FSH occurring in Sertoli cells at the time of transition between proliferative and differentiated states. •FSH response is studied in proteoglycans-depleted 20day-old Sertoli cells.•Alteration of cell membrane proteoglycans reduces the FSH receptor/Gs coupling.•Cell PGs are involved in the recruitment/activation of a PP2A-like activity.•Cell PGs, through retention of PP2A activity, stabilize FSHR/Gs coupling.•Depletion of Cell PGs decreases basal ERK phosphorylation.