Semaphorin controls epidermal morphogenesis by stimulating mRNA translation via eIF2alpha in Caenorhabditis elegans.
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.
Nukazuka
Akira
A
Division of Biological Science, Nagoya University Graduate School of Science, Chikusa-ku, Nagoya 464-8602, Japan.
Fujisawa
Hajime
H
Inada
Toshifumi
T
Oda
Yoichi
Y
Takagi
Shin
S
D020413:3' Untranslated Regions / Q000378:metabolism; D051339:Actin Depolymerizing Factors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D004817:Epidermis / Q000254:growth & development*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D009024:Morphogenesis / Q000235:genetics*; D010766:Phosphorylation; D014176:Protein Biosynthesis; D039961:Semaphorins / Q000378:metabolism*; D019892:eIF-2 Kinase / Q000378:metabolism
D020413:3' Untranslated Regions; D051339:Actin Depolymerizing Factors; D029742:Caenorhabditis elegans Proteins; D015852:Eukaryotic Initiation Factor-2; D008840:Microfilament Proteins; D039961:Semaphorins; D019892:eIF-2 Kinase; C495209:UNC-60 protein, C elegans