Recycling of transferrin receptors and heparan sulfate proteoglycans in a rat parathyroid cell line.

We examined recycling of heparan sulfate (HS) proteoglycans and transferrin receptor (Tf-R) in a rat parathyroid cell line. While extracellular Ca2+ concentration ([Ca2+]e) regulates the recycling of HS proteoglycans in parathyroid cells, such that HS proteoglycans only recycle when [Ca2+]e is lowered below physiological levels, recycling of Tf-R occurs equally well both in 0.05 mM (low) and 2 mM (high) [Ca2+]e. Inhibiting endocytosis chemically with phenylarsine oxide or at low temperature (4 degrees C) did not abolish the effects of changing [Ca2+]e on HS proteoglycans in the recycling compartment even though transport of HS proteoglycans from the Golgi complex to the cell surface was inhibited in low [Ca2+]e. Microtubules are not involved in the recycling of HS proteoglycans or of Tf-R since nocodazole did not affect these processes. Inhibiting the increase of intracellular Ca2+ by an intracellular Ca2+ chelator sustained recycling of HS proteoglycans even in the presence of high [Ca2+]e. These observations show that the exocytosis pathway of HS proteoglycans in the recycling compartment is specifically regulated by [Ca2+]e, whereas that for constitutive secretion is not. Therefore, the recycling of HS proteoglycans may be directly related to some functions of parathyroid cells regulated by [Ca2+]e. Although the mechanism by which [Ca2+]e regulates the exocytosis and recycling of HS proteoglycans is uncertain, it is suggested that an increase of intracellular Ca2+ is necessary, but not necessarily sufficient, for inhibiting their exocytosis.