The calcium-sensing receptor is localized in caveolin-rich plasma membrane domains of bovine parathyroid cells.
Parathyroid cells have an intracellular machinery for parathyroid hormone (PTH) secretion that is inversely regulated by the extracellular calcium concentration (Ca2+o). The recently characterized Ca2+o-sensing receptor (CaR) is a G protein-coupled, seven-transmembrane receptor mediating the inhibitory effects of high Ca2+o on PTH secretion. The CaR's precise cell surface localization and the signal transduction pathway(s) mediating its inhibitory effects on PTH secretion have not been characterized fully. Here, we demonstrate that the CaR resides within caveolin-rich membrane domains in bovine parathyroid cells. Chief cells within bovine parathyroid glands exhibit a similar pattern of staining for caveolin-1 and for alkaline phosphatase, a glucosylphosphatidylinositol-anchored protein often enriched in caveolae. Purified caveolin-enriched membrane fractions (CEMF) from bovine parathyroid cells are highly enriched in the CaR and alkaline phosphatase. Other signaling proteins, including Gq/11, eNOS, and several protein kinase C isoforms (i.e. alpha, delta, and zeta), are also present in CEMF. Activation of the CaR by high Ca2+o increases tyrosine phosphorylation of caveolin-1 in CEMF, suggesting that CaR-mediated signal transduction potentially involved in Ca2+o-regulated processes in parathyroid cells occur in caveolae-like domains.
Endocrine-Hypertension Division and Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
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D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D051242:Caveolin 1; D022461:Caveolins; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D008565:Membrane Proteins / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010280:Parathyroid Glands / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D013499:Surface Properties; D014443:Tyrosine / Q000378:metabolism
D051242:Caveolin 1; D022461:Caveolins; D008565:Membrane Proteins; D010281:Parathyroid Hormone; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D011493:Protein Kinase C; D000469:Alkaline Phosphatase; D002118:Calcium