Active Ran regulates anillin function during cytokinesis

Mol Biol Cell. 2017 Nov 15;28(24):3517-3531. doi: 10.1091/mbc.E17-04-0253. Epub 2017 Sep 20.

Abstract

Cytokinesis cleaves a cell into two daughters at the end of mitosis, and must be spatially coordinated with chromosome segregation to prevent aneuploidy. The dogma is that the mitotic spindle governs the assembly and constriction of an actomyosin ring. Here, we reveal a function for active Ran in spatially restricting the ring. Our model is that during anaphase, "free" importins, whose gradient inversely correlates with active Ran and chromatin position, function as a molecular ruler for the recruitment and localization of anillin, a contractile protein and a crucial regulator of cytokinesis. We found that decreasing Ran-GTP levels or tethering active Ran to the equatorial membrane affects anillin's localization and causes cytokinesis phenotypes. Anillin contains a conserved nuclear localization signal (NLS) at its C-terminus that binds to importin-β and is required for cortical polarity and cytokinesis. Mutating the NLS decreases anillin's cortical affinity, causing it to be more dominantly regulated by microtubules. Anillin contains a RhoA-GTP binding domain, which autoinhibits the NLS and the neighboring microtubule-binding domain, and RhoA-GTP binding may relieve this inhibition during mitosis. Retention of the C-terminal NLS in anillin homologues suggests that this is a conserved mechanism for controlling anillin function.

MeSH terms

  • Animals
  • Cells, Cultured
  • Cytokinesis / physiology
  • HeLa Cells
  • Humans
  • Karyopherins / metabolism*
  • Mice
  • Microfilament Proteins / metabolism*
  • Microtubules / metabolism
  • Mitosis
  • Nuclear Localization Signals / metabolism
  • Spindle Apparatus / metabolism
  • beta Karyopherins / metabolism
  • ran GTP-Binding Protein / metabolism*
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Karyopherins
  • Microfilament Proteins
  • Nuclear Localization Signals
  • RAN protein, human
  • actin-binding protein anillin, human
  • beta Karyopherins
  • ran GTP-Binding Protein
  • rhoA GTP-Binding Protein