Role of the cytoskeleton in extracellular calcium-regulated PTH release.
The calcium-sensing receptor (CaR) mediates the effects of extracellular calcium ([Ca(2+)](o)) on PTH release, such that increasing levels of [Ca(2+)](o) inhibit PTH secretion through poorly defined mechanisms. In the present studies, immunocytochemical analysis demonstrated that F-actin, PTH, CaR, and caveolin-1 are colocalized at the apical secretory pole of PT cells, and subcellular fractionation of PT cells showed these proteins to be present within the secretory granule fraction. High [Ca(2+)](o) caused F-actin, PTH, and caveolin-1 to move to the apical pole of the cells. Depolymerization of F-actin by cytochalasin reduced the actin network and induced redistribution of actin/caveolin-1 to a dispersed pattern within the cell. The F-actin-severing compounds, latrunculin and cytochalasin, significantly increased PTH secretion, while the actin polymerizing agent, jasplakinolide, substantially inhibited PTH secretion. We have demonstrated that in polarized PT cells, the F-actin cytoskeleton is involved in the regulation of PTH secretion and is critical for inhibition of PTH secretion by high calcium.
Quinn
Stephen J
SJ
Division of Endocrinology, Diabetes and Hypertension and the Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. squinn@rics.bwh.harvard.edu
Kifor
Olga
O
Kifor
Imre
I
Butters
Robert R
RR
Brown
Edward M
EM
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D045604:Extracellular Fluid / Q000378:metabolism; D010280:Parathyroid Glands / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism*; D022142:Secretory Vesicles / Q000378:metabolism*
D003598:Cytoskeletal Proteins; D010281:Parathyroid Hormone; D002118:Calcium