IQGAP1 functions as a modulator of dishevelled nuclear localization in Wnt signaling

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 i...

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Bibliographic Details
Published in:PloS one 2013-04, Vol.8 (4), p.e60865-e60865
Main Authors: Goto, Toshiyasu, Sato, Atsushi, Shimizu, Masahiro, Adachi, Shungo, Satoh, Kiyotoshi, Iemura, Shun-ichiro, Natsume, Tohru, Shibuya, Hiroshi
Format: Article
Language:English
Subjects:
Active Transport, Cell Nucleus
Adaptor Proteins, Signal Transducing - metabolism
Animals
Biology
Cell adhesion & migration
Cell Nucleus - metabolism
Cytoplasm
Depletion
Dishevelled protein
Dishevelled Proteins
Embryo, Nonmammalian - cytology
Embryo, Nonmammalian - metabolism
Embryogenesis
Embryonic development
Embryonic growth stage
Embryos
Gene expression
Gene Expression Regulation
Genes
HEK293 Cells
Humans
IQGAP1 protein
Kinases
Localization
Medical research
Mice
Molecular modelling
NIH 3T3 Cells
Nuclei
Phosphoproteins - metabolism
Protein Binding
Proteins
ras GTPase-Activating Proteins - metabolism
Rodents
Signal Transduction
Signaling
Transcription activation
Wnt protein
Wnt Proteins - metabolism
Xenopus
Xenopus - embryology
Xenopus laevis
Xenopus Proteins
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0060865