Bradley R S, Cowin P, Brown A M
Department of Cell Biology and Anatomy, Cornell University Medical College, New York, New York 10021.
J Cell Biol. 1993 Dec;123(6 Pt 2):1857-65. doi: 10.1083/jcb.123.6.1857.
The Wnt-1 gene plays an essential role in fetal brain development and encodes a secreted protein whose signaling mechanism is presently unknown. In this report we have investigated intracellular mechanisms by which the Wnt-1 gene induces morphological changes in PC12 pheochromocytoma cells. PC12 cells expressing Wnt-1 show increased steady-state levels of the adhesive junction protein plakoglobin, and an altered distribution of this protein within the cell. This effect appears similar to a modulation of the plakoglobin homolog, Armadillo, that occurs in Drosophila embryos in response to the Wnt-1 homolog, wingless (Riggleman, B., P. Schedl, and E. Wieschaus. 1990. Cell. 63:549-560). In addition, PC12/Wnt-1 cells show elevated expression of E-cadherin and increased calcium-dependent cell-cell adhesion. These results imply evolutionary conservation of cellular responses to Wnt-1/wingless and indicate that in certain cell types Wnt-1 may act to modulate cell adhesion mechanisms.
Wnt-1基因在胎儿大脑发育中起重要作用,编码一种分泌蛋白,其信号传导机制目前尚不清楚。在本报告中,我们研究了Wnt-1基因诱导PC12嗜铬细胞瘤细胞形态变化的细胞内机制。表达Wnt-1的PC12细胞显示黏附连接蛋白斑珠蛋白的稳态水平增加,且该蛋白在细胞内的分布发生改变。这种效应似乎类似于果蝇胚胎中因Wnt-1同源物无翅蛋白(wingless)而发生的斑珠蛋白同源物犰狳蛋白(Armadillo)的调节作用(Riggleman, B., P. Schedl, and E. Wieschaus. 1990. Cell. 63:549 - 560)。此外,PC12/Wnt-1细胞显示E-钙黏蛋白表达升高,钙依赖性细胞间黏附增加。这些结果表明细胞对Wnt-1/无翅蛋白反应的进化保守性,并表明在某些细胞类型中,Wnt-1可能起到调节细胞黏附机制的作用。