经典Wnt信号通路诱导粘着斑和整合素β-1内吞作用。
Canonical Wnt signaling induces focal adhesion and Integrin beta-1 endocytosis.
作者信息
Tejeda-Muñoz Nydia, Morselli Marco, Moriyama Yuki, Sheladiya Pooja, Pellegrini Matteo, De Robertis Edward M
机构信息
Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles 90095-1662, USA.
Dipartimento di Scienze Chimiche, della Vita e della Sostenibilità Ambientale, University of Parma, Parm, Italy.
出版信息
iScience. 2022 Mar 19;25(4):104123. doi: 10.1016/j.isci.2022.104123. eCollection 2022 Apr 15.
During canonical Wnt signaling, the Wnt receptor complex is sequestered together with glycogen synthase kinase 3 (GSK3) and Axin inside late endosomes, known as multivesicular bodies (MVBs). Here, we present experiments showing that Wnt causes the endocytosis of focal adhesion (FA) proteins and depletion of Integrin β 1 (ITGβ1) from the cell surface. FAs and integrins link the cytoskeleton to the extracellular matrix. Wnt-induced endocytosis caused ITGβ1 depletion from the plasma membrane and was accompanied by striking changes in the actin cytoskeleton. protease protection assays in cultured cells showed that ITGβ1 was sequestered within membrane-bounded organelles that corresponded to Wnt-induced MVBs containing GSK3 and FA-associated proteins. An model using embryos dorsalized by mRNA showed that ITGβ1 depletion decreased Wnt signaling. The finding of a crosstalk between two major signaling pathways, canonical Wnt and focal adhesions, should be relevant to human cancer and cell biology.
在经典Wnt信号传导过程中，Wnt受体复合物与糖原合酶激酶3（GSK3）和Axin一起被隔离在内体晚期，即多囊泡体（MVBs）中。在此，我们展示的实验表明，Wnt会导致粘着斑（FA）蛋白的内吞作用以及整联蛋白β1（ITGβ1）从细胞表面的耗竭。粘着斑和整联蛋白将细胞骨架与细胞外基质相连。Wnt诱导的内吞作用导致ITGβ1从质膜上耗竭，并伴随着肌动蛋白细胞骨架的显著变化。培养细胞中的蛋白酶保护试验表明，ITGβ1被隔离在膜结合细胞器内，这些细胞器与Wnt诱导的含有GSK3和FA相关蛋白的MVBs相对应。使用经mRNA背侧化的胚胎的模型表明，ITGβ1的耗竭会降低Wnt信号传导。经典Wnt和粘着斑这两个主要信号通路之间存在相互作用的这一发现，应该与人类癌症和细胞生物学相关。
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