A Wnt-CKIvarepsilon-Rap1 pathway regulates gastrulation by modulating SIPA1L1, a Rap GTPase activating protein.

Published

Journal Article

Noncanonical Wnt signals control morphogenetic movements during vertebrate gastrulation. Casein kinase I epsilon (CKIvarepsilon) is a Wnt-regulated kinase that regulates Wnt/beta-catenin signaling and has a beta-catenin-independent role(s) in morphogenesis that is poorly understood. Here we report the identification of a CKIvarepsilon binding partner, SIPA1L1/E6TP1, a GAP (GTPase activating protein) of the Rap small GTPase family. We show that CKIvarepsilon phosphorylates SIPA1L1 to reduce its stability and thereby increase Rap1 activation. Wnt-8, which activates CKIvarepsilon, enhances the CKIvarepsilon-dependent phosphorylation and degradation of SIPA1L1. In early Xenopus or zebrafish development, inactivation of the Rap1 pathway results in abnormal gastrulation and a shortened anterior-posterior axis. Although CKIvarepsilon also transduces Wnt/beta-catenin signaling, inhibition of Rap1 does not alter beta-catenin-regulated gene expression. Our data demonstrate a role for CKIvarepsilon in noncanonical Wnt signaling and indicate that Wnt regulates morphogenesis in part through CKIvarepsilon-mediated control of Rap1 signaling.

Full Text

Duke Authors

Cited Authors

  • Tsai, I-C; Amack, JD; Gao, Z-H; Band, V; Yost, HJ; Virshup, DM

Published Date

  • March 2007

Published In

Volume / Issue

  • 12 / 3

Start / End Page

  • 335 - 347

PubMed ID

  • 17336901

Pubmed Central ID

  • 17336901

Electronic International Standard Serial Number (EISSN)

  • 1878-1551

International Standard Serial Number (ISSN)

  • 1534-5807

Digital Object Identifier (DOI)

  • 10.1016/j.devcel.2007.02.009

Language

  • eng