MAPK/ERK activity is required for the successful progression of mitosis in sea urchin embryos

Dev Biol. 2017 Jan 15;421(2):194-203. doi: 10.1016/j.ydbio.2016.11.018. Epub 2016 Nov 29.

Abstract

Using sea urchin embryos, we demonstrate that the MEK/MAPK/ERK cascade is essential for the proper progression of the cell cycle. Activation of a limited fraction of MAPK/ERK is required between S-phase and M-phase. Neither DNA replication nor CDK1 activation are impacted by the inhibition of this small active MAPK/ERK fraction. Nonetheless, the chromatin and spindle organisations are profoundly altered. Early morphological disorders induced by the absence of MAPK/ERK activation are correlated with an important inhibition of global protein synthesis and modification in the cyclin B accumulation profile. After appearance of morphological disorders, there is an increase in the level of the inhibitor of protein synthesis, 4E-BP, and, ultimately, an activation of the spindle checkpoint. Altogether, our results suggest that MAPK/ERK activity is required for the synthesis of (a) protein(s) implicated in an early step of chromatin /microtubule attachment. If this MAPK/ERK-dependent step is not achieved, the cell activates a new checkpoint mechanism, involving the reappearance of 4E-BP that maintains a low level of protein translation, thus saving cellular energy.

Keywords: Cell cycle checkpoint; Embryonic cell division; MAPK/ERK pathway.

MeSH terms

  • Animals
  • Biological Evolution
  • Butadienes / pharmacology
  • CDC2 Protein Kinase / metabolism
  • Carrier Proteins / metabolism
  • Cell Division / drug effects
  • Chromatin / metabolism
  • Cyclin B / metabolism
  • DNA Replication / drug effects
  • Embryo, Nonmammalian / cytology*
  • Embryo, Nonmammalian / drug effects
  • Embryo, Nonmammalian / enzymology*
  • Enzyme Activation / drug effects
  • Fertilization / drug effects
  • MAP Kinase Signaling System* / drug effects
  • Microtubules / drug effects
  • Microtubules / metabolism
  • Mitosis* / drug effects
  • Nitriles / pharmacology
  • Ovum / cytology
  • Ovum / drug effects
  • Phosphorylation / drug effects
  • Protein Biosynthesis / drug effects
  • Sea Urchins / cytology*
  • Sea Urchins / drug effects
  • Sea Urchins / embryology*

Substances

  • Butadienes
  • Carrier Proteins
  • Chromatin
  • Cyclin B
  • Nitriles
  • U 0126
  • CDC2 Protein Kinase