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Wdpcp, a PCP protein required for ciliogenesis, regulates directional cell migration and cell polarity by direct modulation of the actin cytoskeleton
Journal article   Open access

Wdpcp, a PCP protein required for ciliogenesis, regulates directional cell migration and cell polarity by direct modulation of the actin cytoskeleton

Cheng Cui, Bishwanath Chatterjee, Thomas P Lozito, Zhen Zhang, Richard J Francis, Hisato Yagi, Lisa M Swanhart, Subramaniam Sanker, Deanne Francis, Qing Yu, …
PLoS biology, v 11(11), pp e1001720-e1001720
Nov 2013
DOI: https://doi.org/10.1371/journal.pbio.1001720
PMID: 24302887
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1371/journal.pbio.1001720View
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Abstract

Cilia - physiology Amino Acid Sequence Cell Polarity Actin Cytoskeleton - metabolism Mice, Inbred C57BL Cells, Cultured Molecular Sequence Data Zebrafish Time-Lapse Imaging Mice, Inbred C3H Protein Transport Animals DNA Mutational Analysis Base Sequence Focal Adhesions - metabolism Mice Polymorphism, Single Nucleotide Septins - metabolism Cytoskeletal Proteins - physiology Wnt Signaling Pathway Cell Movement
Planar cell polarity (PCP) regulates cell alignment required for collective cell movement during embryonic development. This requires PCP/PCP effector proteins, some of which also play essential roles in ciliogenesis, highlighting the long-standing question of the role of the cilium in PCP. Wdpcp, a PCP effector, was recently shown to regulate both ciliogenesis and collective cell movement, but the underlying mechanism is unknown. Here we show Wdpcp can regulate PCP by direct modulation of the actin cytoskeleton. These studies were made possible by recovery of a Wdpcp mutant mouse model. Wdpcp-deficient mice exhibit phenotypes reminiscent of Bardet-Biedl/Meckel-Gruber ciliopathy syndromes, including cardiac outflow tract and cochlea defects associated with PCP perturbation. We observed Wdpcp is localized to the transition zone, and in Wdpcp-deficient cells, Sept2, Nphp1, and Mks1 were lost from the transition zone, indicating Wdpcp is required for recruitment of proteins essential for ciliogenesis. Wdpcp is also found in the cytoplasm, where it is localized in the actin cytoskeleton and in focal adhesions. Wdpcp interacts with Sept2 and is colocalized with Sept2 in actin filaments, but in Wdpcp-deficient cells, Sept2 was lost from the actin cytoskeleton, suggesting Wdpcp is required for Sept2 recruitment to actin filaments. Significantly, organization of the actin filaments and focal contacts were markedly changed in Wdpcp-deficient cells. This was associated with decreased membrane ruffling, failure to establish cell polarity, and loss of directional cell migration. These results suggest the PCP defects in Wdpcp mutants are not caused by loss of cilia, but by direct disruption of the actin cytoskeleton. Consistent with this, Wdpcp mutant cochlea has normal kinocilia and yet exhibits PCP defects. Together, these findings provide the first evidence, to our knowledge, that a PCP component required for ciliogenesis can directly modulate the actin cytoskeleton to regulate cell polarity and directional cell migration.

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Biology
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