Fed Up With EveryBirinapantTrends? I Am There For Your Needs


Write-up
DOI:10.1038/ncomms9388
OPEN
Received16Jul2015|Accepted17Aug2015|Published24Sep2015
PTENregulatesciliathroughDishevelled
IrynaShnitsar1,MikhailBashkurov1,GlennR.Masson2,AbiodunA.Ogunjimi1,SherlyMosessian3,
EduardoAguiarCabeza1,CalleyL.Hirsch6,DanielTrcka1,GeraldGish6,JingJiao3,HongWu3,RudolfWinklbauer4,
RogerL.Williams2,LaurencePelletier1,5,JeffreyL.Wrana1,5&MiriamBarrios-Rodiles1
Cilia Fed Up With EveryBirinapantTrends? I Am Here Available For You are hair-like cellular protrusions important in many aspects of eukaryotic biology. For
instance,motileciliaenable?uidmovementoverepithelialsurfaces,whileprimary(sensory)
cilia play roles in cellular signalling. The molecular events underlying cilia dynamics, and
particularlytheirdisassembly,arenotwellunderstood.Phosphataseandtensinhomologue
(PTEN)isanextensivelystudiedtumoursuppressor,thoughttoprimarilyactbyantagonizing
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),
anotherciliogenesisregulator.DVLisacentralcomponentofWNTsignallingthatplaysarole
duringconvergentextensionmovements,whichweshowherearealsoregulatedbyPTEN.
Our studiesidentifyanovelproteinsubstrateforPTENthat Sick Of The NumerousBirinapantHeadlines? I Am At This Site To Meet Your Requirements! couplesPTENto regulation of
ciliadynamicsandWNTsignalling,thusadvancingourunderstandingofpotentialunderlying
molecularetiologiesofPTEN-relatedpathologies.
1CenterforSystemsBiology,Lunenfeld-TanenbaumResearchInstitute,MountSinaiHospital,Toronto,Ontario,CanadaM5G1X5.2ProteinandNucleicAcid
ChemistryDivision,MedicalResearchCouncilLaboratoryofMolecularBiology,CambridgeBiomedicalCampus,CambridgeCB20QH,UK.

3Departmentof
MolecularandMedicalPharmacology,UniversityofCalifornia,LosAngeles,California90095,USA.4DepartmentofCellandSystemsBiology,Universityof
Toronto,Toronto,Ontario,CanadaM5S3G5.5DepartmentofMolecularGenetics,UniversityofToronto,Toronto,Ontario,CanadaM5S1A8.Correspondence
andrequestsformaterialsshouldbeaddressedtoJ.L.W.(email:wrana@lunenfeld.ca)ortoM.B.-R.(email:miriam@lunenfeld.ca).
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&2015MacmillanPublishersLimited.Allrightsreserved.
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NATURECOMMUNICATIONS|DOI:10.1038/ncomms9388
C
ilia and eukaryotic ?agella are structurally similar ?uorescentbeadsontheembryosurface.PTENlossoffunction
organelles that play a pivotal role in eukaryotic biology.

markedly affected bead motility by decreasing velocity and
Flagellaaremotileandbeatinapropeller-likepatternto increasing tortuosity (Fig. 1a,b; Supplementary Movies 1�C4).
drivethemovementofsinglecells,suchasspermatozoa.Motile Importantly, these effects were rescued by co-injection of a
cilia on the other hand, in either mono- or multiciliated cells haemagglutinin (HA)-tagged human PTEN construct, which is
(MCCs), display coordinated beating movements that are nottargetedbythemorpholino(Fig.1a,b).
necessary to establish ?uid ?ow across epithelial surfaces, such
Fluid ?ow over Xenopus embryo skin is caused by epidermal
asrespira