Prabakaran D, Ahima R S, Harney J W, Berry M J, Larsen P R, Arvan P
Beth Israel Hospital, Harvard Medical School, Boston, MA, USA.
J Cell Sci. 1999 Apr;112 ( Pt 8):1247-56. doi: 10.1242/jcs.112.8.1247.
Polarized trafficking signals may be interpreted differently in different cell types. In this study, we have compared the polarized trafficking of different proteins expressed endogenously in primary porcine thyroid epithelial cells to similar proteins expressed in MDCK cells. As in MDCK cells, NH4Cl treatment of filter-grown thyrocytes caused mis-sorted soluble proteins to exhibit enhanced secretion to the apical medium. In independent studies, thrombospondin 1 (a thyroid basolaterally secreted protein) was secreted basolaterally from MDCK cells. Likewise, the 5'-deiodinase (a thyroid basolateral membrane protein) encoded by the DIO1 gene was also distributed basolaterally in transfected MDCK cells. Consistent with previous reports, when the secretion of human growth hormone (an unglycosylated regulated secretory protein) was examined from transfected MDCK cells, the release was nonpolarized. However, transfected thyrocytes secreted growth hormone apically in a manner dependent upon zinc addition. Moreover, two additional regulated secretory proteins expressed in thyrocytes, thyroglobulin (the major endogenous glycoprotein) and parathyroid hormone (an unglycosylated protein expressed transiently), were secreted apically even in the absence of zinc. We hypothesize that while cellular mechanisms for interpreting polarity signals are generally similar between thyrocytes and MDCK cells, thyrocytes allow for specialized packaging of regulated secretory proteins for apical delivery, which does not require glycosylation but may involve availability of certain ions as well as appropriate intracellular compartmentation.
极化运输信号在不同细胞类型中可能有不同的解读方式。在本研究中，我们比较了原代猪甲状腺上皮细胞中内源性表达的不同蛋白质与在MDCK细胞中表达的相似蛋白质的极化运输情况。与MDCK细胞一样，用氯化铵处理滤膜培养的甲状腺细胞会导致分选错误的可溶性蛋白质向顶端培养基的分泌增加。在独立研究中，血小板反应蛋白1（一种甲状腺基底外侧分泌的蛋白质）从MDCK细胞中基底外侧分泌。同样，由DIO1基因编码的5'-脱碘酶（一种甲状腺基底外侧膜蛋白）在转染的MDCK细胞中也分布在基底外侧。与先前的报道一致，当检测转染的MDCK细胞中人生长激素（一种未糖基化的受调控分泌蛋白）的分泌时，其释放是非极化的。然而，转染的甲状腺细胞以依赖于添加锌的方式将生长激素分泌到顶端。此外，甲状腺细胞中表达的另外两种受调控分泌蛋白，甲状腺球蛋白（主要的内源性糖蛋白）和甲状旁腺激素（一种瞬时表达的未糖基化蛋白），即使在没有锌的情况下也会分泌到顶端。我们推测，虽然甲状腺细胞和MDCK细胞之间解读极性信号的细胞机制通常相似，但甲状腺细胞允许对受调控分泌蛋白进行特殊包装以进行顶端递送，这不需要糖基化，但可能涉及某些离子的可用性以及适当的细胞内区室化。
