Giarré M, Semënov M V, Brown A M
Department of Cell Biology and Anatomy, Cornell University Medical College, New York, New York 10021, USA.
Ann N Y Acad Sci. 1998 Oct 23;857:43-55. doi: 10.1111/j.1749-6632.1998.tb10106.x.
The Wnt proteins constitute a large family of secreted signaling factors that performed a wide variety of inductive and regulatory functions in embryonic and postnatal development. In mammals, these include crucial roles in morphogenesis of the central nervous system, kidneys, limbs, and mammary glands. In recent years, much progress has been made in identifying components of the intracellular Wnt-1 signal transduction pathway through studies in Drosophila, C. elegans, Xenopus, and mammalian systems. Several features of this pathway are remarkably well conserved in evolution. A key component of the Wnt pathway is the cytoplasmic protein beta-catenin, whose stability is increased as a result of Wnt signaling. Although morphological effects of Wnt-1 in cell culture are seen in only a limited number of cell lines, we show here that responsiveness to Wnt-1 at the biochemical level is a common property of both epithelial and mesenchymal cells. The increased abundance of beta-catenin may have at least two functional consequences, depending on the subcellular localization of the protein. In some cell lines that respond to Wnt-1, there is a significant increase in the beta-catenin fraction associated with the plasma membrane, where the protein acts as a component of cell-cell adhesive junctions. In other cell types, the major effect of Wnt signaling is an increase in the cytosolic pool of beta-catenin. Increased abundance of this pool has recently been correlated with entry of beta-catenin into the nucleus, where the protein forms complexes with Tcf transcription factors and is thought to modulate the expression of specific genes. The dual consequences of Wnt signaling on cell adhesion and/or gene expression provide at least two potential mechanisms by which this key pathway can function in the regulation of morphogenesis.
Wnt蛋白构成了一个分泌型信号因子大家族，在胚胎发育和出生后发育中发挥着广泛的诱导和调节功能。在哺乳动物中，这些功能包括在中枢神经系统、肾脏、四肢和乳腺的形态发生中发挥关键作用。近年来，通过对果蝇、秀丽隐杆线虫、非洲爪蟾和哺乳动物系统的研究，在确定细胞内Wnt-1信号转导途径的组成成分方面取得了很大进展。该途径的几个特征在进化过程中显著保守。Wnt途径的一个关键成分是细胞质蛋白β-连环蛋白，其稳定性因Wnt信号传导而增加。虽然Wnt-1在细胞培养中的形态学效应仅在有限数量的细胞系中可见，但我们在此表明，上皮细胞和间充质细胞在生化水平上对Wnt-1的反应性是一种共同特性。β-连环蛋白丰度的增加可能至少有两个功能后果，这取决于该蛋白的亚细胞定位。在一些对Wnt-1有反应的细胞系中，与质膜相关的β-连环蛋白部分显著增加，该蛋白在质膜处作为细胞间黏附连接的一个成分发挥作用。在其他细胞类型中，Wnt信号传导的主要作用是增加β-连环蛋白的胞质池。最近，该池丰度的增加与β-连环蛋白进入细胞核相关，在细胞核中该蛋白与Tcf转录因子形成复合物，并被认为可调节特定基因的表达。Wnt信号传导对细胞黏附和/或基因表达的双重后果提供了至少两种潜在机制，通过这些机制，这一关键途径可在形态发生的调节中发挥作用。
