Beta-catenin asymmetry is regulated by PLA1 and retrograde traffic in C. elegans stem cell divisions.
Asymmetric division is an important property of stem cells. In Caenorhabditis elegans, the Wnt/beta-catenin asymmetry pathway determines the polarity of most asymmetric divisions. The Wnt signalling components such as beta-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 A(1) (PLA(1)), a poorly characterized lipid-metabolizing enzyme, controls the subcellular localizations of beta-catenin in the terminal asymmetric divisions of epithelial stem cells (seam cells). In mutants of ipla-1, a single C. elegans PLA(1) gene, cortical beta-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 beta-catenin to ipla-1 mutants. We propose that membrane trafficking regulated by ipla-1 provides a mechanism to control the cortical asymmetry of beta-catenin.
Kanamori
Takahiro
T
Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Inoue
Takao
T
Sakamoto
Taro
T
Gengyo-Ando
Keiko
K
Tsujimoto
Masafumi
M
Mitani
Shohei
S
Sawa
Hitoshi
H
Aoki
Junken
J
Arai
Hiroyuki
H
D000818:Animals; D001692:Biological Transport; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002452:Cell Count; D002455:Cell Division; D019070:Cell Lineage; D016764:Cell Polarity; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005260:Female; D017238:Genes, Helminth; D016153:Genes, Suppressor; D020662:Guanine Nucleotide Exchange Factors; D050505:Mutant Proteins / Q000302:isolation & purification / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D054466:Phospholipases A1 / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D013347:Subcellular Fractions / Q000378:metabolism; D014844:Vulva / Q000166:cytology; D051176:beta Catenin / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D003598:Cytoskeletal Proteins; D020662:Guanine Nucleotide Exchange Factors; D050505:Mutant Proteins; C120104:WRM-1 protein, C elegans; D051176:beta Catenin; D054466:Phospholipases A1; D020691:rab GTP-Binding Proteins