Semaphorin controls epidermal morphogenesis by stimulating mRNA translation via eIF2alpha in Caenorhabditis elegans.

Genes & Development
Akira NukazukaShin Takagi

Abstract

Conserved semaphorin-plexin signaling systems govern various aspects of animal development, including axonal guidance in vertebrates and epidermal morphogenesis in Caenorhabditis elegans. Here we provide in vivo evidence that stimulation of mRNA translation via eukaryotic initiation factor 2alpha (eIF2alpha) is an essential downstream event of semaphorin signaling in C. elegans. In semaphorin/plexin mutants, a marked elevation in the phosphorylation of eIF2alpha is observed, which causes translation repression and is causally related to the morphological epidermal phenotype in the mutants. Conversely, removal of constraints on translation by genetically reducing the eIF2alpha phosphorylation largely bypasses requirement for the semaphorin signal in epidermal morphogenesis. We also identify an actin-depolymerizing factor/cofilin, whose expression in the mutants is predominantly repressed, as a major translational target of semaphorin signaling. Thus, our results reveal a physiological significance for translation of mRNAs for cytoskeletal regulators, linking environmental cues to cytoskeletal rearrangement during cellular morphogenesis in vivo.

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Citations

Jan 29, 2011·Molecular Neurobiology·Sreenivasan Ponnambalam, Mario Alberghina
Sep 29, 2011·Nature Communications·Akira NukazukaShin Takagi
Apr 17, 2008·Genes & Development·Andrew D Chisholm
Aug 25, 2010·Molecular and Cellular Biology·Xianrong R Mao, C Michael Crowder
May 26, 2012·PloS One·Ayako OkazakiShin Takagi
Mar 14, 2020·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Hiroki TanakaShin Takagi
Mar 30, 2013·Wiley Interdisciplinary Reviews. Developmental Biology·Andrew D Chisholm, Tiffany I Hsiao
Aug 28, 2020·ELife·Fabrice BesnardMarie-Anne Félix
Oct 16, 2010·Biochemical and Biophysical Research Communications·Gabriele WagnerAnnette Borchers
Jul 29, 2008·Development·Britta J Eickholt

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