Extracellular calcium regulates distribution and transport of heparan sulfate proteoglycans in a rat parathyroid cell line

The regulation of the cellular distribution of proteoglycans in a clonal rat parathyroid cell line by extracellular Ca2+ concentrations (Ca2+]e) was studied. Proteoglycans synthesized by the cells metabolically labeled with 35S]sulfate have been shown to be almost exclusively heparan sulfate (HS) proteoglycans (Yanagishita, M., Brandi, M.L., and Sakaguchi, K. (1989) J. Biol. Chem. 264, 15714-15720), which are generally associated with the plasma membrane. The proportion of HS proteoglycans on the cell surface was approximately 20% in 2.1 mM (high) Ca2+]e, whereas it increased to 50-60% in 0.05 mM (low) Ca2+]e. Cell-associated HS proteoglycans redistribute in response to changing Ca2+]e with a t 1/2 less than 4 min; HS proteoglycans appear on the cell surface as Ca2+]e decreases and disappear from the cell surface as Ca2+]e increases. Further, HS proteoglycans on the cell surface recycle to and from an intracellular compartment approximately 10 times before their degradation in low Ca2+]e but do not recycle in high Ca2+]e. The distribution of newly synthesized HS proteoglycans is regulated by Ca2+]e but is independent of Ca2+]e during biosynthesis. In low Ca2+]e, at least 50% of the HS proteoglycans pulse-labeled for 10 min are transported from the Golgi complex to the cell surface or to the recycling compartment with a t 1/2 of approximately 20 min. Another approximately 10% appear on the cell surface in either low or high Ca2+]e in a compartment with a long half-life. Addition of Mg2+ or Ba2+ to the low Ca2+]e cultures had little effect on the distribution of HS proteoglycans. These observations suggest that Ca2+]e specifically regulates the distribution and recycling of cell-associated HS proteoglycans in the parathyroid cells.