Why SerineEvolved Our Lives 2011

was expected for PTEN Serine interaction
(Supplementary Fig. 3c,d). Endogenous PTEN and DVL2 also
interacted in the human retinal epithelial cell line (hTERT-RPE1)
that assembles cilia in vitro (Fig. 3b). In addition, endogenous
PTEN partially co-localized with ectopically expressed DVL in
areas adjacent to BBs in hTERT-RPE1 (information not proven) and
with Xenopus Dishevelled (Dsh) in MCCs (Supplementary
Fig. 2c). To much better visualize co-localization between PTEN and
DshinXenopusMCCs,wealsousedaDVLmutantlackingthe
DIXdomain(dDIX-Dsh).Thismutantretainsproperlocalization
totheBBareaanddoesnotformaggregates,whicharefrequently
twenty
detected when WT Dsh is overexpressed . Interestingly, in
XenopusMCCsPTENanddDIX-Dsh-GFPwerelocalizednextto
BBs marked by Centrin-RFP and have been usually observed in
adjacent regions that partially overlapped.

As a result, overlapping
PTENandDshsignals(SupplementaryFig.2c,whitearrows),as
very well HMG-CoA Reductase inhibitor structure as adjacent localization (magenta arrows) had been readily
obvious.
Previousreportsindicatethatciliadisassemblyistriggeredby
casein kinase 1 (CK1e)-dependent DVL2 phosphorylation on
serine 143 (Fig. 4c) that promotes DVL2 interaction with Polo-
like kinase-1 (PLK1), which subsequently activates the HEF-1/
PTEN´┐ŻCDsh interaction regulates morphogenetic processes. Aurora kinaseA/HDAC6pathway,triggeringtubulindeacetyla-
DVLisaparticularlyintriguingPTENpartner,asitiscrucialfor tion and cilia disassembly35,36. These observations prompted us
ciliaformationinbothXenopusandmice. Inparticular, equivalent totestwhetherPTENcanregulatephospho-DVL2levels.

Firstwe
on the results of PTEN knockdown described above, loss of in contrast the amounts of phosphorylated serine 143 (pS143) on
DVL has an effect on apical docking of http://www.selleckchem.com/FLT-3.html BBs and overexpression of the DVL2 in hTERT-RPE1 cells throughout the formation of cilia in
twenty
dominant-negativeDVLinducesrotationalpolaritydefects .To controlcellsversuscellslackingPTEN.ThisrevealedthatPTEN
NATURE COMMUNICATIONS |6:8388|DOI: 10.1038/ncomms9388 |www.nature.com/naturecommunications
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