Cdc42 regulates GSK-3β and adenomatous polyposis coli to control cell polarity
Abstract
Cell polarity is a fundamental property of all cells. In higher eukaryotes, the small GTPase Cdc42, acting through a Par6-atypical protein kinase C (aPKC) complex, is required to establish cellular asymmetry during epithelial morphogenesis, asymmetric cell division and directed cell migration. However, little is known about what lies downstream of this complex. Here we show, through the use of primary rat astrocytes in a cell migration assay, that Par6-PKCzeta interacts directly with and regulates glycogen synthase kinase-3beta (GSK-3beta) to promote polarization of the centrosome and to control the direction of cell protrusion. Cdc42-dependent phosphorylation of GSK-3beta occurs specifically at the leading edge of migrating cells, and induces the interaction of adenomatous polyposis coli (Apc) protein with the plus ends of microtubules. The association of Apc with microtubules is essential for cell polarization. We conclude that Cdc42 regulates cell polarity through the spatial regulation of GSK-3beta and Apc. This role for Apc may contribute to its tumour-suppressor activity.
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APC has known functions in cellular motility and cytoskeletal integrity.
“The known functions of APC in cellular motility and cytoskeletal integrity [22, 23]”
From Modeling APC mutagenesis and familial adenomatous polyposis using human iPS cells (2018) · cites this paper as [22]
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Modeling APC mutagenesis and familial adenomatous polyposis using human iPS cells
Sommer, C. A., Capilla, A., Molina-Estevez, F. J., Gianotti-Sommer, A., Skvir, N., Caballero, I., Chowdhury, S., & Mostoslavsky, G. (2018) · PLOS ONE · doi:10.1371/journal.pone.0200657 · Cited by 39 · see citing works
“The known functions of APC in cellular motility and cytoskeletal integrity [22, 23] prompted us to investigate whether expression of a defective copy of APC could affect cell polarity.”
Background
- Authors
- Etienne-Manneville, S., & Hall, A.
- Affiliations
- Cancer Research UK (GB)
- Corresponding author
- Hall, Alan
- Venue
- Nature
- Published
- 2003-01-29
- Volume
- 421
- Issue
- 6924
- Pages
- 753-756
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2002897207
- Cited by
- 835
- References
- 1
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 9 · 2023: 19 · 2022: 10 · 2021: 17 · 2020: 21 · 2019: 22 · 2018: 22 · 2017: 23 · 2016: 22 · 2015: 31 · 2014: 30 · 2013: 36 · 2012: 32
- FWCI
- 25.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- Cdc42, GSK3β, adenomatous polyposis coli, cell polarity, Par6, protein kinase C zeta, cell migration, microtubules, asymmetric cell division, tumor suppression, astrocytes, GTPase signaling
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Protein Kinase C zeta, Animals, Astrocytes, Cell Movement, Cells, Cultured, Cytoskeletal Proteins, Microtubules, Phosphorylation, Protein Kinase C, Proteins, Trans-Activators, Cell Polarity, Centrosome, cdc42 GTP-Binding Protein, Adenomatous Polyposis Coli Protein, Glycogen Synthase Kinase 3, beta Catenin, Rats
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