Transforming growth factor β2 is released from PC12 cells via the regulated pathway of secretion

Transforming growth factor beta2 (TGF-beta2), a prototypic member of a large superfamily of multifunctional cytokines, is expressed by neurons and glial cells. Its subcellular compartmentalization and release from neurons, however, are largely unknown. Here we show, that TGF-beta2 colocalizes with the trans-Golgi network marker TGN38 and a marker molecule for secretory granules, chromogranin B (CgB), in PC12 cells. Similarly, primary hippocampal neurons show coloealization of TGN38 and TGF-beta2. A substantial amount of endogenous as well as transfected TGF-beta2 in PC12 cells comigrates with CgB on an equilibrium gradient, suggesting eostorage in secretory granules. TGF-beta3 biological activity peaks in identical fractions. Depolarization of PC 12 cells with high potassium triggers colocalization of CgB and TGF-beta2 at the cell surface, suggesting their regulated corelease from secretory granules. High potassium also liberates biologically active TGF-beta from PC 12 cells and primary neurons. Our results indicate that a substantial portion of TGF-beta2 is secreted by the regulated secretory pathway in PC 12 cells and hippocampal neurons. (C) 2003 Elsevier Science (USA). All rights reserved.