β-Catenin asymmetry is regulated by PLA1 and retrograde traffic in C. elegans stem cell divisions

• Takahiro Kanamori ^[1] ; Takao Inoue ^[5] ; Taro Sakamoto ^[2] ; Keiko Gengyo-Ando ^[3] ; Masafumi Tsujimoto ^[6] ; Shohei Mitani ^[3] ; Hitoshi Sawa ^[4] ; Junken Aoki ^[3] ; Hiroyuki Arai ^[5]
  1. [1] University of Tokyo

     University of Tokyo

     Japón

     
  2. [2] Kitasato University

     Kitasato University

     Japón

     
  3. [3] Japan Science and Technology Agency

     Japan Science and Technology Agency

     Japón

     
  4. [4] RIKEN Center for Developmental Biology

     RIKEN Center for Developmental Biology

     Chuo-ku, Japón

     
  5. [5] Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan; CREST, Japan Science and Technology Agency, Saitama, Japan
  6. [6] Laboratory of Cellular Biochemistry, RIKEN, Saitama, Japan

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 27, Nº. 12, 2008, págs. 1647-1657
• Idioma: inglés
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• Resumen

  • Asymmetric division is an important property of stem cells. In Caenorhabditis elegans, the Wnt/β-catenin asymmetry pathway determines the polarity of most asymmetric divisions. The Wnt signalling components such as β-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 β-catenin in the terminal asymmetric divisions of epithelial stem cells (seam cells). In mutants of ipla-1, a single C. elegans PLA1 gene, cortical β-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 β-catenin to ipla-1 mutants. We propose that membrane trafficking regulated by ipla-1 provides a mechanism to control the cortical asymmetry of β-catenin.