ArticleThe Journal of biological chemistry2011
Par6B and atypical PKC regulate mitotic spindle orientation during epithelial morphogenesis.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 132 citations in OpenAlex.
- Polarity Gene PARD6B Promotes Tumor Growth of Colorectal Cancer via Increasing MYC Expression.Cancer science · 2025Article
- Polarity protein Par6 facilitates the processive phosphorylation of Lgl via a dynamic interaction with aPKC.Communications biology · 2025Article
- The PAR6B-PRKCI-PAR3 complex influences alveolar regeneration in patients with the emphysema subtype of chronic obstructive pulmonary disease.Stem cell research & therapy · 2025Article
- The dynamics of tubulogenesis in development and disease.Development (Cambridge, England) · 2025Review
- Article
- Cell polarity proteins promote macropinocytosis in response to metabolic stress.Nature communications · 2024Article
- Reduced LHFPL3-AS2 lncRNA expression is linked to altered epithelial polarity and proliferation, and to ileal ulceration in Crohn disease.Scientific reports · 2023Article
- Membrane recruitment of the polarity protein Scribble by the cell adhesion receptor TMIGD1.Communications biology · 2023Article
- Multicellular rosettes link mesenchymal-epithelial transition to radial intercalation in the mouse axial mesoderm.Developmental cell · 2023Article
- Involvement of Dmp1 in the Precise Regulation of Hair Bundle Formation in the Developing Cochlea.Biology · 2023Article
- PHLPP1 regulates CFTR activity and lumen expansion through AMPK.Development (Cambridge, England) · 2022Article
- Depletion of the apical endosome in response to viruses and bacterial toxins provides cell-autonomous host defense at mucosal surfaces.Cell host & microbe · 2022Article
- Insights Into Mechanisms of Oriented Division From Studies in 3D Cellular Models.Frontiers in cell and developmental biology · 2022Review
- Rho and Rab Family Small GTPases in the Regulation of Membrane Polarity in Epithelial Cells.Frontiers in cell and developmental biology · 2022Review
- A proximity proteomics screen in three-dimensional spheroid cultures identifies novel regulators of lumen formation.Scientific reports · 2021Article
- CD13 orients the apical-basal polarity axis necessary for lumen formation.Nature communications · 2021Article
- Distinct types of stem cell divisions determine organ regeneration and aging in hair follicles.Nature aging · 2021Article
- Girdin is a component of the lateral polarity protein network restricting cell dissemination.PLoS genetics · 2020Article
- The Dual Roles of the Atypical Protein Kinase Cs in Cancer.Cancer cell · 2019Review
- Deficiency in the phosphatase PHLPP1 suppresses osteoclast-mediated bone resorption and enhances bone formation in mice.The Journal of biological chemistry · 2019Article
25 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Cdc42 plays an evolutionarily conserved role in promoting cell polarity and is indispensable during epithelial morphogenesis. To further investigate the role of Cdc42, we have used a three-dimensional matrigel model, in which single Caco-2 cells develop to form polarized cysts. Using this system, we previously reported that Cdc42 controls mitotic spindle orientation during cell division to correctly position the apical surface in a growing epithelial structure. In the present study, we have investigated the specific downstream effectors through which Cdc42 controls this process. Here, we report that Par6B and its binding partner, atypical protein kinase C (aPKC), are required to regulate Caco-2 morphogenesis. Depletion or inhibition of Par6B or aPKC phenocopies the loss of Cdc42, inducing misorientation of the mitotic spindle, mispositioning of the nascent apical surface, and ultimately, the formation of aberrant cysts with multiple lumens. Mechanistically, Par6B and aPKC function interdependently in this context. Par6B localizes to the apical surface of Caco-2 cysts and is required to recruit aPKC to this compartment. Conversely, aPKC protects Par6B from proteasomal degradation, in a kinase-independent manner. In addition, we report that depletion or inhibition of aPKC induces robust apoptotic cell death in Caco-2 cells, significantly reducing both cyst size and number. Cell survival and apical positioning depend upon different thresholds of aPKC expression, suggesting that they are controlled by distinct downstream pathways. We conclude that Par6B and aPKC control mitotic spindle orientation in polarized epithelia and, furthermore, that aPKC coordinately regulates multiple processes to promote morphogenesis.
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