Canonical Wnt signaling induces focal adhesion and Integrin beta-1 endocytosis
- PMID: 35402867
- PMCID: PMC8987407
- DOI: 10.1016/j.isci.2022.104123
Canonical Wnt signaling induces focal adhesion and Integrin beta-1 endocytosis
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 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. In situ 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 in vivo model using Xenopus embryos dorsalized by Wnt8 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.
Keywords: Cell biology; Developmental biology; Omics.
© 2022 The Author(s).
Conflict of interest statement
The authors declare no competing interests.
Figures
![None](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/8987407/bin/fx1.gif)
![Figure 1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/8987407/bin/gr1.gif)
![Figure 2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/8987407/bin/gr2.gif)
![Figure 3](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/8987407/bin/gr3.gif)
![Figure 4](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/8987407/bin/gr4.gif)
![Figure 5](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/8987407/bin/gr5.gif)
![Figure 6](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/8987407/bin/gr6.gif)
![Figure 7](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/8987407/bin/gr7.gif)
Similar articles
-
Wnt signaling requires sequestration of glycogen synthase kinase 3 inside multivesicular endosomes.Cell. 2010 Dec 23;143(7):1136-48. doi: 10.1016/j.cell.2010.11.034. Cell. 2010. PMID: 21183076 Free PMC article.
-
Arginine methylation is required for canonical Wnt signaling and endolysosomal trafficking.Proc Natl Acad Sci U S A. 2018 Jun 5;115(23):E5317-E5325. doi: 10.1073/pnas.1804091115. Epub 2018 May 17. Proc Natl Acad Sci U S A. 2018. PMID: 29773710 Free PMC article.
-
Wnt, GSK3, and Macropinocytosis.Subcell Biochem. 2022;98:169-187. doi: 10.1007/978-3-030-94004-1_9. Subcell Biochem. 2022. PMID: 35378708 Review.
-
Wnt canonical pathway activates macropinocytosis and lysosomal degradation of extracellular proteins.Proc Natl Acad Sci U S A. 2019 May 21;116(21):10402-10411. doi: 10.1073/pnas.1903506116. Epub 2019 May 6. Proc Natl Acad Sci U S A. 2019. PMID: 31061124 Free PMC article.
-
Cell Biology of Canonical Wnt Signaling.Annu Rev Cell Dev Biol. 2021 Oct 6;37:369-389. doi: 10.1146/annurev-cellbio-120319-023657. Epub 2021 Jul 1. Annu Rev Cell Dev Biol. 2021. PMID: 34196570 Review.
Cited by
-
The PMA phorbol ester tumor promoter increases canonical Wnt signaling via macropinocytosis.Elife. 2023 Oct 30;12:RP89141. doi: 10.7554/eLife.89141. Elife. 2023. PMID: 37902809 Free PMC article.
-
KCNQ potassium channels modulate Wnt activity in gastro-oesophageal adenocarcinomas.Life Sci Alliance. 2023 Sep 25;6(12):e202302124. doi: 10.26508/lsa.202302124. Print 2023 Dec. Life Sci Alliance. 2023. PMID: 37748809 Free PMC article.
-
Multi-cancer analysis reveals universal association of oncogenic LBH expression with DNA hypomethylation and WNT-Integrin signaling pathways.Cancer Gene Ther. 2023 Sep;30(9):1234-1248. doi: 10.1038/s41417-023-00633-y. Epub 2023 Jun 2. Cancer Gene Ther. 2023. PMID: 37268816 Free PMC article.
-
Identification of R-Spondin Gene Signature Predictive of Metastatic Progression in BRAFV600E-Positive Papillary Thyroid Cancer.Cells. 2022 Dec 29;12(1):139. doi: 10.3390/cells12010139. Cells. 2022. PMID: 36611933 Free PMC article.
-
Multi-omics analysis of sarcospan overexpression in mdx skeletal muscle reveals compensatory remodeling of cytoskeleton-matrix interactions that promote mechanotransduction pathways.Skelet Muscle. 2023 Jan 6;13(1):1. doi: 10.1186/s13395-022-00311-x. Skelet Muscle. 2023. PMID: 36609344 Free PMC article.
References
-
- Albrecht L.V., Tejeda-Muñoz N., Bui M.H., Cicchetto A.C., Di Biagio D., Colozza G., Schmid E., Piccolo S., Christofk H.R., De Robertis E.M. GSK3 inhibits macropinocytosis and lysosomal activity through the Wnt destruction complex machinery. Cell Rep. 2020;32:107973. doi: 10.1016/j.celrep.2020.107973. PMID: 32726636. - DOI - PMC - PubMed
Grants and funding
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous