PTEN regulates cilia through Dishevelled

Iryna Shnitsar, Mikhail Bashkurov, Glenn R. Masson, Abiodun A. Ogunjimi, Sherly Mosessian, Eduardo Aguiar Cabeza, Calley L. Hirsch, Daniel Trcka, Gerald Gish, Jing Jiao, Hong Wu, Rudolf Winklbauer, Roger L. Williams, Laurence Pelletier, Jeffrey L. Wrana () and Miriam Barrios-Rodiles ()
Additional contact information
Iryna Shnitsar: Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
Mikhail Bashkurov: Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
Glenn R. Masson: Medical Research Council Laboratory of Molecular Biology, Cambridge Biomedical Campus
Abiodun A. Ogunjimi: Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
Sherly Mosessian: University of California
Eduardo Aguiar Cabeza: Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
Calley L. Hirsch: Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
Daniel Trcka: Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
Gerald Gish: Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
Jing Jiao: University of California
Hong Wu: University of California
Rudolf Winklbauer: University of Toronto
Roger L. Williams: Medical Research Council Laboratory of Molecular Biology, Cambridge Biomedical Campus
Laurence Pelletier: Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
Jeffrey L. Wrana: Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
Miriam Barrios-Rodiles: Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: Abstract Cilia are hair-like cellular protrusions important in many aspects of eukaryotic biology. For instance, motile cilia enable fluid movement over epithelial surfaces, while primary (sensory) cilia play roles in cellular signalling. The molecular events underlying cilia dynamics, and particularly their disassembly, are not well understood. Phosphatase and tensin homologue (PTEN) is an extensively studied tumour suppressor, thought to primarily act by antagonizing PI3-kinase signalling. Here we demonstrate that PTEN plays an important role in multicilia formation and cilia disassembly by controlling the phosphorylation of Dishevelled (DVL), another ciliogenesis regulator. DVL is a central component of WNT signalling that plays a role during convergent extension movements, which we show here are also regulated by PTEN. Our studies identify a novel protein substrate for PTEN that couples PTEN to regulation of cilia dynamics and WNT signalling, thus advancing our understanding of potential underlying molecular etiologies of PTEN-related pathologies.

Date: 2015
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DOI: 10.1038/ncomms9388

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