TPPP acts downstream of RhoA-ROCK-LIMK2 to regulate astral microtubule organization and spindle orientation

J Cell Sci. 2012 Mar 15;125(Pt 6):1579-90. doi: 10.1242/jcs.096818. Epub 2012 Feb 10.

Abstract

The actin cytoskeleton in eukaryotic cells undergoes drastic rearrangement during mitosis. The changes to the actin cytoskeleton are most obvious in the adherent cells, where the actin stress fibres are disassembled, and the cortical actin network becomes more prominent with concomitant increase in cell rigidity as cells round up and enter mitosis. Although the regulatory connections between the actin cytoskeleton and the early mitotic events are apparent, the mechanisms that govern these links are not well understood. Here, we report that LIMK1 and LIMK2, the downstream effectors of RhoA and ROCK, regulate centrosome integrity and astral microtubule organization, respectively. Surprisingly, LIMK1 and cofilin are not involved downstream of RhoA and ROCK in the regulation of astral microtubule organization. Instead, we find that LIMK2 acts through TPPP in the regulation of astral microtubule organization, whereas both LIMK1 and LIMK2 affect centrosome focusing. Both phenotypes are tightly coupled to spindle orientation in the mitotic cells. Thus, our results reveal a new regulatory link between the actin cytoskeleton and the mitotic spindle during the early stages of mitosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / genetics
  • Actin Cytoskeleton / metabolism
  • Actin Cytoskeleton / physiology
  • HeLa Cells
  • Humans
  • Lim Kinases / genetics
  • Lim Kinases / physiology
  • Metaphase / genetics
  • Microtubule Proteins / genetics
  • Microtubule Proteins / physiology*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology
  • Spindle Apparatus / genetics
  • Spindle Apparatus / physiology*
  • rho-Associated Kinases / genetics
  • rho-Associated Kinases / physiology
  • rhoA GTP-Binding Protein / genetics
  • rhoA GTP-Binding Protein / physiology

Substances

  • Microtubule Proteins
  • Nerve Tissue Proteins
  • TPPP protein, human
  • LIMK2 protein, human
  • Lim Kinases
  • ROCK1 protein, human
  • rho-Associated Kinases
  • rhoA GTP-Binding Protein