title: IQGAP1 functions as a modulator of dishevelled nuclear localization in Wnt signaling.
abstract: Dishevelled (DVL) is a central factor in the Wnt signaling pathway, which is highly conserved among various organisms. DVL plays important roles in transcriptional activation in the nucleus, but the molecular mechanisms underlying their nuclear localization remain unclear. In the present study, we identified IQGAP1 as a regulator of DVL function. In Xenopus embryos, depletion of IQGAP1 reduced Wnt-induced nuclear accumulation of DVL, and expression of Wnt target genes during early embryogenesis. The domains in DVL and IQGAP1 that mediated their interaction are also required for their nuclear localization. Endogenous expression of Wnt target genes was reduced by depletion of IQGAP1 during early embryogenesis, but notably not by depletion of other IQGAP family genes. Moreover, expression of Wnt target genes caused by depletion of endogenous IQGAP1 could be rescued by expression of wild-type IQGAP1, but not IQGAP1 deleting DVL binding region. These results provide the first evidence that IQGAP1 functions as a modulator in the canonical Wnt signaling pathway.
authors.affiliation: Department of Molecular Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Goto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sato
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shimizu
authors.forename: Shungo
authors.initials: S
authors.lastname: Adachi
authors.forename: Kiyotoshi
authors.initials: K
authors.lastname: Satoh
authors.forename: Shun-ichiro
authors.initials: S
authors.lastname: Iemura
authors.forename: Tohru
authors.initials: T
authors.lastname: Natsume
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shibuya
mesh_terms: D021581:Active Transport, Cell Nucleus; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D000072261:Dishevelled Proteins; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D014981:Xenopus / Q000196:embryology; D029867:Xenopus Proteins; D020703:ras GTPase-Activating Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C000606586:DVL1 protein, Xenopus; D000072261:Dishevelled Proteins; C101203:IQ motif containing GTPase activating protein 1; D010750:Phosphoproteins; D051153:Wnt Proteins; D029867:Xenopus Proteins; D020703:ras GTPase-Activating Proteins