Centralspindlin Explained

Centralspindlin is a motor complex implicated in cell division. It contributes to virtually every step in cytokinesis,[1] It is highly conserved in animal cells as a component of the spindle midzone and midbody.[2] Centralspindlin is required for the assembly of the mitotic spindle[3] as well as for microtubule bundling and anchoring of midbody microtubules to the plasma membrane. This complex is also implicated in tethering the spindle apparatus to the plasma membrane during cytokinesis[4] This interaction permits cleavage furrow ingression. In addition, centralspindlin's interaction with the ESCRT III allows for abscission to occur.

Structure

Centralspindlin is a heterotetramer consisting of two different subunit proteins:

  1. A KIF23 dimer (Kinesin 6 motor protein, also known as MKLP1 in mammals and ZEN-4 in C. elegans)

Consists of a motor domain linked to a parallel coiled coil and a globular region by a linker

  1. A RACGAP1 dimer (Also known as MgcRacGAP in mammals or CYK-4 in C. elegans)

Contains a coiled-coil and an important RhoGAP domainBoth KIF23 and RacGAP1 dimerize via their parallel coiled coil domain.[5] Centralspindlin oligomerizes in order to link the mitotic spindle with the plasma membrane The sequences mediating interactions between KIF23 and RacGAP1 are highly variable between species. However, a high affinity interaction between these subunits is essential for the proper functioning of the Centralspindlin complex.

Subunits

KIF23 interacts with microtubules at sites of overlap, linking the centralspindlin complex to the mitotic spindle.RacGAP1 recruits ECT2 to the central spindle. ECT2 is a Guanine nucleotide-exchange factor for RhoA. Cytokinesis is initiated when RhoA is activated by ECT2.[6] RacGAP1 is also involved in tethering the central spindle to the plasma membrane. Without this interaction, cytokinesis cannot occur.

Interactions

Notes and References

  1. Glotzer, Michael. "Cytokinesis: Centralspindlin Moonlights as a Membrane Anchor", Current Biology, 18 February 2013
  2. Glotzer, Michael " The 3Ms of central spindle assembly: microtubules, motors and MAPs", Nature, January 2009
  3. Nature Publishing Group. "Research Highlights", Cell Migration Consortium, 2009. Retrieved on 01 March 2014.
  4. Lekomtsev et al. "Centralspindlin links the mitotic spindle to the plasma membrane during cytokinesis", Nature, 13 December 2012
  5. Pavicic-Kaltenbrunner et al. "Cooperative assembly of CYK-4/MgcRacGAP and ZEN-4/MKLP1 to form the centralspindlin complex", Molecular Biology of the Cell, 17 October 2007
  6. Tatsumoto et al "Human Ect2 Is an Exchange Factor for Rho Gtpases, Phosphorylated in G2/M Phases, and Involved in Cytokinesis", Journal of Cell Biology, 29 November 1999
  7. Web site: Cytokinesis microtubule organisers at a glance. J Cell Sci.
  8. Yuce et al. "An ECT2–centralspindlin complex regulates the localization and function of RhoA", Journal of Cell Biology, 15 August 2005
  9. Gene Editing Rat Resource Center "Gene-Term Annotation Report", Retrieved on 01 March 2014
  10. Douglas et al. "Aurora B and 14-3-3 Coordinately Regulate Clustering of Centralspindlin during Cytokinesis", Current Biology, 25 May 2010
  11. Lee KY, Esmaeili B, Zealley B, Mishima M . Direct interaction between centralspindlin and PRC1 reinforces mechanical resilience of the central spindle . Nature Communications . 6 . 7290 . 2015 . 26088160 . 10.1038/ncomms8290 . 4557309. 2015NatCo...6.7290L .

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