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 b 1 (ITGb1) from the cell surface. FAs and integrins link the cytoskeleton to the extracellular matrix. Wnt-induced endocytosis caused ITGb1 depletion from the plasma membrane and was accompanied by striking changes in the actin cytoskeleton. In situ protease protection assays in cultured cells showed that ITGb1 was sequestered within membrane-bounded organelles that corresponded to Wnt-induced MVBs containing GSK3 and FA-associated proteins. An in vivo model using Xenopus embryos dorsalized by Wnt8 mRNA showed that ITGb1 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.

Canonical Wnt signaling induces focal adhesion and Integrin beta-1 endocytosis / Tejeda-Muñoz, Nydia; Morselli, Marco; Moriyama, Yuki; Sheladiya, Pooja; Pellegrini, Matteo; De Robertis, Edward M.. - In: ISCIENCE. - ISSN 2589-0042. - 25:4(2022), p. 104123. [10.1016/j.isci.2022.104123]

Canonical Wnt signaling induces focal adhesion and Integrin beta-1 endocytosis

Morselli, Marco;
2022

Abstract

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 b 1 (ITGb1) from the cell surface. FAs and integrins link the cytoskeleton to the extracellular matrix. Wnt-induced endocytosis caused ITGb1 depletion from the plasma membrane and was accompanied by striking changes in the actin cytoskeleton. In situ protease protection assays in cultured cells showed that ITGb1 was sequestered within membrane-bounded organelles that corresponded to Wnt-induced MVBs containing GSK3 and FA-associated proteins. An in vivo model using Xenopus embryos dorsalized by Wnt8 mRNA showed that ITGb1 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.
Canonical Wnt signaling induces focal adhesion and Integrin beta-1 endocytosis / Tejeda-Muñoz, Nydia; Morselli, Marco; Moriyama, Yuki; Sheladiya, Pooja; Pellegrini, Matteo; De Robertis, Edward M.. - In: ISCIENCE. - ISSN 2589-0042. - 25:4(2022), p. 104123. [10.1016/j.isci.2022.104123]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2920749
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