Article
- The EMBO Journal (2008) 27, 1647 - 1657
- doi:10.1038/emboj.2008.102
Published online: 22 May 2008
Subject Categories:
-Catenin asymmetry is regulated by PLA1 and retrograde traffic in C. elegans stem cell divisionsEMBO Open
Takahiro Kanamori1,2, Takao Inoue1,3, Taro Sakamoto4, Keiko Gengyo-Ando3,5, Masafumi Tsujimoto2, Shohei Mitani3,5, Hitoshi Sawa6,7, Junken Aoki8,9 and Hiroyuki Arai1,3
- Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
- Laboratory of Cellular Biochemistry, RIKEN, Saitama, Japan
- CREST, Japan Science and Technology Agency, Saitama, Japan
- School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan
- Department of Physiology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan
- Laboratory for Cell Fate Decision, RIKEN Center for Developmental Biology, Kobe, Japan
- Department of Biology, Graduate School of Science, Kobe University, Kobe, Japan
- Department of Molecular & Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan
- PRESTO, Japan Science and Technology Agency, Saitama, Japan
Correspondence to:
Hiroyuki Arai, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Tel: +81 3 5841 4720; Fax: +81 3 3818 3173; E-mail: harai@mol.f.u-tokyo.ac.jp
Received 10 January 2008; Accepted 28 April 2008
Abstract
Asymmetric division is an important property of stem cells. In Caenorhabditis elegans, the Wnt/
-catenin asymmetry pathway determines the polarity of most asymmetric divisions. The Wnt signalling components such as
-catenin localize asymmetrically to the cortex of mother cells to produce two distinct daughter cells. However, the molecular mechanism to polarize them remains to be elucidated. Here, we demonstrate that intracellular phospholipase A1 (PLA1), a poorly characterized lipid-metabolizing enzyme, controls the subcellular localizations of
-catenin in the terminal asymmetric divisions of epithelial stem cells (seam cells). In mutants of ipla-1, a single C. elegans PLA1 gene, cortical
-catenin is delocalized and the asymmetry of cell-fate specification is disrupted in the asymmetric divisions. ipla-1 mutant phenotypes are rescued by expression of ipla-1 in seam cells in a catalytic activity-dependent manner. Furthermore, our genetic screen utilizing ipla-1 mutants reveals that reduction of endosome-to-Golgi retrograde transport in seam cells restores normal subcellular localization of
-catenin to ipla-1 mutants. We propose that membrane trafficking regulated by ipla-1 provides a mechanism to control the cortical asymmetry of
-catenin.
Keywords:
- asymmetric divisions,
- C. elegans,
- phospholipase,
- retrograde trafficking,
- the Wnt/
-catenin asymmetry pathway
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