Involvement of p114-RhoGEF and Lfc in Wnt-3a- and Dishevelled-induced RhoA Activation and Neurite Retraction in N1E-115 Mouse Neuroblastoma Cells.
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Involvement of p114-RhoGEF and Lfc in Wnt-3a- and Dishevelled-induced RhoA Activation and Neurite Retraction in N1E-115 Mouse Neuroblastoma Cells.

Mol Biol Cell. 2010 Sep 1;

Authors: Tsuji T, Ohta Y, Kanno Y, Hirose K, Ohashi K, Mizuno K

Monitoring Editor: Kozo Kaibuchi The Wnt-induced planar cell polarity (PCP) signaling pathway is essential for polarized cell migration and morphogenesis. Dishevelled (Dvl) and its binding protein Daam1 mediate RhoA activation in this pathway. WGEF, a member of the Rho-guanine nucleotide exchange factor (Rho-GEF) family, was shown to play a role in Wnt-induced RhoA activation in Xenopus embryos. However, it has remained unknown which member(s) of a Rho-GEF family are involved in Wnt/Dvl-induced RhoA activation in mammalian cells. Here we identified p114-RhoGEF and Lfc (also called GEF-H1) as the Rho-GEFs responsible for Wnt-3a-induced RhoA activation in N1E-115 mouse neuroblastoma cells. We screened for Rho-GEF-silencing short-hairpin RNAs (shRNAs) that are capable of suppressing Dvl-induced neurite retraction in N1E-115 cells, and found that p114-RhoGEF and Lfc shRNAs, but not WGEF shRNA, suppressed Dvl- and Wnt-3a-induced neurite retraction. p114-RhoGEF and Lfc shRNAs also inhibited Dvl- and Wnt-3a-induced RhoA activation, and p114-RhoGEF and Lfc proteins were capable of binding to Dvl and Daam1. Additionally, the Dvl-binding domains of p114-RhoGEF and Lfc inhibited Dvl-induced neurite retraction. Our results suggest that p114-RhoGEF and Lfc are critically involved in Wnt-3a- and Dvl-induced RhoA activation and neurite retraction in N1E-115 cells.

PMID: 20810787 [PubMed - as supplied by publisher]

Read the complete post at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=20810787&dopt=Abstract

Posted 3 Sep 2010 5:10 AM by pubmed: neuroblastoma
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