TY - JOUR
T1 - PTEN regulates cilia through Dishevelled
AU - Shnitsar, Iryna
AU - Bashkurov, Mikhail
AU - Masson, Glenn R.
AU - Ogunjimi, Abiodun A.
AU - Mosessian, Sherly
AU - Cabeza, Eduardo Aguiar
AU - Hirsch, Calley L.
AU - Trcka, Daniel
AU - Gish, Gerald
AU - Jiao, Jing
AU - Wu, Hong
AU - Winklbauer, Rudolf
AU - Williams, Roger L.
AU - Pelletier, Laurence
AU - Wrana, Jeffrey L.
AU - Barrios-Rodiles, Miriam
N1 - Funding Information:
We thank Melanie Pye and Yuliya Khomchuk for the assistance with mouse work, Dr Yu (Sunny) Liu for help with preparation of the heatmap of LUMIER data, Silkan Bains for help with cell culture work, Dr Alexander Weiss for the modified pCAGIP vector, Drs Valbona Luga and Rohit Bose for insightful discussions. Dr Liliana Attisano for critical reading of the manuscript. Dr Michael Parsons at the Flow Cytometry Facility and Douglas Holmyard at the Electron Microscopy Facility for training, technical support and help in generating ‘Xenopus MCC’ featured image (Lunenfeld-Tanenbaum Research Institute). Drs Brigit L. Hogan (Duke University Medical Center) for generously providing FOXJ1-CreER mouse line, J. Wallingford (University of Texas at Austin) for the CLAMP-GFP construct and R. Winklbauer as well as his lab members, especially Jason Wen and Olivia Luu, for assistance with Xenopus work. J.L.W. is supported by the Ontario Ministry of Research and Innovation, ORF-GL2 program and Canadian Institutes of Health Research (Foundation Program), L.P. is supported by Canadian Institutes of Health Research (CIHR) (grants MOP-123468 and MOP-130507), R.L.W. is funded by UK Medical Research Council (MC_U105184308RW) and R.W. is supported by CIHR (grant MOP-53075). J.L.W. and L.P. are supported by Krembil Foundation.
Publisher Copyright:
© 2015 Macmillan Publishers Limited. All rights reserved.
PY - 2015/9/24
Y1 - 2015/9/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84942107663&partnerID=8YFLogxK
U2 - 10.1038/ncomms9388
DO - 10.1038/ncomms9388
M3 - Article
C2 - 26399523
AN - SCOPUS:84942107663
SN - 2041-1723
VL - 6
JO - Nature Communications
JF - Nature Communications
M1 - 8388
ER -