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

Transforming growth factor β2 is released from PC12 cells via the regulated pathway of secretion
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DOI:
10.1016/s1044-7431(02)00023-4
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发表时间:
2003-01-01
影响因子:
3.5
通讯作者:
Unsicker, K
Unsicker, K
中科院分区:
医学3区
文献类型:
--
作者:
Specht, H;Peterziel, H;Unsicker, K

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转化生长因子β 2(TGF-β 2)是多功能细胞因子大超家族的原型成员,由神经元和神经胶质细胞表达。然而,其亚细胞区室化和从神经元释放在很大程度上是未知的。在这里,我们表明,TGF-β 2共定位与trans-Golgi网络标记TGN 38和分泌颗粒的标记分子,嗜铬粒蛋白B(Cg B),在PC 12细胞。类似地,原代海马神经元显示TGN 38和TGF-β 2的共愈合。大量的内源性以及转染的TGF-β 2在PC 12细胞中与CgB在平衡梯度上共迁移,这表明在分泌颗粒中共储存。TGF-β 3生物活性在相同的级分中达到峰值。高钾PC 12细胞的去极化触发CgB和TGF-β 2在细胞表面的共定位,表明它们从分泌颗粒的调节共释放。高钾还从PC 12细胞和原代神经元释放生物活性TGF-β。我们的研究结果表明,TGF-β 2的相当大的一部分是由PC 12细胞和海马神经元的调节分泌途径分泌。(C)2003 Elsevier Science(美国)。All rights reserved.
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.