A Wnt-CKIε-Rap1 pathway regulates gastrulation by modulating SIPA1L1, a rap GTPase activating protein

• Published in: Developmental cell Vol. 12; no. 3; pp. 335 - 347
• Main Authors: TSAI, I-Chun, AMACK, Jeffrey D, GAO, Zhong-Hua, BAND, Vimla, YOST, H. Joseph, VIRSHUP, David M
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Cell Press 01-03-2007
• Subjects: Biological and medical sciences; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Fundamental and applied biological sciences. Psychology; Molecular and cellular biology; Xenopus; Regulation(control); Gastrulation; Enzyme; Triphosphoric monoester hydrolases; Development; dGTPase; Hydrolases; Esterases; GTPase activating protein
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2007.02.009

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