MOLECULAR CHARACTERIZATION OF A SWELLING-INDUCED CHLORIDE CONDUCTANCE REGULATORY PROTEIN, PL(CLN)

Cells maintain control of their volume by the passage of KCl and water across their membranes, but the regulatory proteins are unknown. Expression in Xenopus oocytes of a novel protein, pl(Cln), activated a chloride conductance. We have cloned analogs of pl(Cln), from rat heart and Xenopus ovary. pl(Cln) was identified as an abundant soluble cytosolic protein (similar to 40 kd) that does not immunolocalize with the plasma membrane. pl(Cln) was found in epithelial and cardiac cells, brain, and Xenopus oocytes, forming complexes with soluble actin and other cytosolic proteins. Monoclonal antibodies recognizing pl(Cln) blocked activation of a native hypotonicity-induced chloride conductance (I-Cl.swell) in Xenopus oocytes, suggesting that pin, may link actin-bound cytoskeletal elements to an unidentified volume-sensitive chloride channel. The high degree of sequence conservation and widespread expression of pl(Cln) suggest that it is an important element in cellular volume regulation.