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Dishevelled controls apical docking and planar polarization of basal bodies in ciliated epithelial cells.

ABSTRACT: The planar cell polarity (PCP) signaling system governs many aspects of polarized cell behavior. Here, we use an in vivo model of vertebrate mucociliary epithelial development to show that Dishevelled (Dvl) is essential for the apical positioning of basal bodies. We find that Dvl and Inturned mediate the activation of the Rho GTPase specifically at basal bodies, and that these three proteins together mediate the docking of basal bodies to the apical plasma membrane. Moreover, we find that this docking involves a Dvl-dependent association of basal bodies with membrane-bound vesicles and the vesicle-trafficking protein, Sec8. Once docked, basal bodies again require Dvl and Rho for the planar polarization that underlies directional beating of cilia. These results demonstrate previously undescribed functions for PCP signaling components and suggest that a common signaling apparatus governs both apical docking and planar polarization of basal bodies.

SUBMITTER: Park TJ

PROVIDER: S-EPMC2771675 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

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Dishevelled controls apical docking and planar polarization of basal bodies in ciliated epithelial cells.

Park Tae Joo TJ Mitchell Brian J BJ Abitua Philip B PB Kintner Chris C Wallingford John B JB

Nature genetics 20080615 7

The planar cell polarity (PCP) signaling system governs many aspects of polarized cell behavior. Here, we use an in vivo model of vertebrate mucociliary epithelial development to show that Dishevelled (Dvl) is essential for the apical positioning of basal bodies. We find that Dvl and Inturned mediate the activation of the Rho GTPase specifically at basal bodies, and that these three proteins together mediate the docking of basal bodies to the apical plasma membrane. Moreover, we find that this d ...[more]

PMID: 18552847

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Project description:Mechanical guidance of tissue morphogenesis is an emerging method of regenerative medicine that can be employed to steer functional kidney architecture for the purpose of bioartificial kidney design or renal tissue engineering strategies. In kidney morphogenesis, apical-basal polarization of renal epithelial cells is paramount for tubule formation and subsequent tissue functions like excretion and resorption. In kidney epithelium, polarization is initiated by integrin-mediated cell-matrix adhesion at the cell membrane. Cellular mechanobiology research has indicated that this integrin-mediated adhesion is responsive to matrix stiffness, raising the possibility to use matrix stiffness as a handle to steer cell polarization. Herein, we evaluate apical-basal polarization in response to 2D substates of different stiffness (1, 10, 50 kPa and glass) in Madin Darby Canine Kidney cells (MDCKs), a classic canine-derived cell model of epithelial polarization, and in tubuloid-derived cells, established from human primary cells derived from adult kidney tissue. Our results show that sub-physiological (1 kPa) substrate stiffness with low integrin-based adhesion induces polarization in MDCKs, while MDCKs on supraphysiological (>10 kPa) stiffness remain unpolarized. Inhibition of integrin, indeed, allows for polarization on the supraphysiological substrates, suggesting that increased cellular adhesion on stiff substrates opposes polarization. In contrast, tubuloid-derived cells do not establish apical-basal polarization on 2D substrates, irrespective of substrate stiffness, despite their ability to polarize in 3D environments. Further analysis implies that the 2D cultured tubuloid-derived cells have a diminished mechanosensitive capacity when presented with different substrate stiffnesses due to immature focal adhesions and the absence of a connection between focal adhesions and the cytoskeleton. Overall, this study demonstrates that apical-basal polarization is a complex process, where cell type, the extracellular environment, and both the mechanical and chemical aspects in cell-matrix interactions performed by integrins play a role.

Dataset Information

Dishevelled controls apical docking and planar polarization of basal bodies in ciliated epithelial cells.

Publications

Dishevelled controls apical docking and planar polarization of basal bodies in ciliated epithelial cells.

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