MEK1 inactivates Myt1 to regulate Golgi membrane fragmentation and mitotic entry in mammalian cells

EMBO J. 2013 Jan 9;32(1):72-85. doi: 10.1038/emboj.2012.329. Epub 2012 Dec 14.

Abstract

The pericentriolar stacks of Golgi cisternae are separated from each other in G2 and fragmented extensively during mitosis. MEK1 is required for Golgi fragmentation in G2 and for the entry of cells into mitosis. We now report that Myt1 mediates MEK1's effects on the Golgi complex. Knockdown of Myt1 by siRNA increased the efficiency of Golgi complex fragmentation by mitotic cytosol in permeabilized and intact HeLa cells. Myt1 knockdown eliminated the requirement of MEK1 in Golgi fragmentation and alleviated the delay in mitotic entry due to MEK1 inhibition. The phosphorylation of Myt1 by MEK1 requires another kinase but is independent of RSK, Plk, and CDK1. Altogether our findings reveal that Myt1 is inactivated by MEK1 mediated phosphorylation to fragment the Golgi complex in G2 and for the entry of cells into mitosis. It is known that Myt1 inactivation is required for CDK1 activation. Myt1 therefore is an important link by which MEK1 dependent fragmentation of the Golgi complex in G2 is connected to the CDK1 mediated breakdown of Golgi into tubules and vesicles in mitosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CDC2 Protein Kinase / genetics
  • CDC2 Protein Kinase / metabolism*
  • Female
  • G2 Phase / physiology
  • Gene Knockdown Techniques
  • Golgi Apparatus / enzymology*
  • Golgi Apparatus / metabolism
  • Golgi Apparatus / ultrastructure
  • HeLa Cells
  • Humans
  • MAP Kinase Kinase 1 / genetics
  • MAP Kinase Kinase 1 / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mitosis / physiology*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*

Substances

  • Membrane Proteins
  • Protein-Tyrosine Kinases
  • PKMYT1 protein, human
  • Protein-Serine-Threonine Kinases
  • CDC2 Protein Kinase
  • MAP Kinase Kinase 1