Transforming growth factor beta2 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 colocalization 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 costorage in secretory granules. TGF-beta biological activity peaks in identical fractions. Depolarization of PC12 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 PC12 cells and primary neurons. Our results indicate that a substantial portion of TGF-beta2 is secreted by the regulated secretory pathway in PC12 cells and hippocampal neurons.
Specht
Heike
H
Neuroanatomy and Center for Neurosciences (IZN), University of Heidelberg, Im Neuenheimer Feld 307, 2.OG, D-69120 Heidelberg, Germany.
Peterziel
Heike
H
Bajohrs
Mark
M
Gerdes
Hans Hermann
HH
Krieglstein
Kerstin
K
Unsicker
Klaus
K
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002451:Cell Compartmentation / Q000187:drug effects / Q000502:physiology*; D002864:Chromogranins / Q000378:metabolism; D006023:Glycoproteins; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins; D009420:Nervous System / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D022142:Secretory Vesicles / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D053781:Transforming Growth Factor beta2; D021601:trans-Golgi Network / Q000187:drug effects / Q000378:metabolism
D002864:Chromogranins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C509041:TGFB2 protein, human; C513045:Tgoln2 protein, rat; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D011188:Potassium; D002118:Calcium