IQGAP1 Functions As a Modulator of Dishevelled Nuclear Localization in Wnt Signaling

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Apr 12

PMID 23577172

Citations 19

Authors

Toshiyasu Goto

Atsushi Sato

Masahiro Shimizu

Shungo Adachi

Kiyotoshi Satoh

Shun-Ichiro Iemura

Tohru Natsume

Hiroshi Shibuya

Affiliations

Soon will be listed here.

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.

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