EXPANDING THE PDZD7 INTERACTOME: PDZD7 CONNECTS THE USHER PROTEIN COMPLEX TO WNT SIGNALING AND INTRAFLAGELLAR TRANSPORT
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2014-12-01
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en
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Usher syndrome (USH) is the leading genetic cause of deaf-blindness. Mutations in PDZDl have been found to modify USH, and its gene product PDZ domain-containing 7 (PDZD7) is a paralog of scaffold proteins whirlin and harmonin. Previous studies have connected PDZD7 to the USH interactome, through the interactions with several USH proteins. Previously identified putative interactors include intraflagellar transport (IFT) proteins and molecules involved in the Wnt signaling pathway. Here, we tried to expand and validate the interactome of PDZD7 in relation to these modules. Novel candidate interactors were found in yeast two-hybrid analyses and include Wnt signaling molecules P-catenin, LZTS2, CBY1 and YWHAE, and IFT protein IFT57. Co-localization studies showed that PDZD7 overlaps with CBY1 and YWHAE, but not with p-catenin, which indicate an indirect role for PDZD7 in Wnt signaling. Possibly, PDZD7 plays a role in the formation of a signaling hub, as several regulators of Wnt signaling were identified as putative interactors. While co-immunoprecipitation experiments failed for IFT57, they revealed interactions between PDZD7 and IFT25 and IFT27. This indicates that PDZD7 may be responsible for the pre-assembly and/or trafficking of the USH2 complex. In this report we provide the first evidence that IFT and Wnt signaling may be linked to USH.
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Faculteit der Sociale Wetenschappen