Centralspindlin

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.[1][2] 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.[1]

Structure

Centralspindlin is a heterotetramer consisting of two different subunit proteins:[1]

  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 domain

Both KIF23 and RacGAP1 dimerize via their parallel coiled coil domain.[2][5] Centralspindlin oligomerizes in order to link the mitotic spindle with the plasma membrane[1] 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.[5]

Subunits

KIF23 interacts with microtubules at sites of overlap,[2] linking the centralspindlin complex to the mitotic spindle. RacGAP1 recruits ECT2 to the central spindle.[3] 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.[4]

Interactions
  • A glance at the busy complex [7]
  • Interacts with RhoA and Rac during furrow ingression[4][8]
  • Recruits cytokinetic effector proteins such as ECT2[6][9]
  • Binds microtubule plus-end overlaps characteristic of the central spindle through its KIF23 subunit[2]
  • Recruits the ESCRT III complex in late cytokinesis[1]
  • Promotes cortical accumulation of F-actin and myosin through its RACGAP1 subunit[8]
  • Stabilized through interactions with Aurora B kinase[10]
  • Negatively regulated by 14-3-3[10]
  • RacGAP1 binds to PRC1 microtubule crosslinker, an interaction that is crucial for maintaining the stability of the spindle midzone.[11]

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. 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
  5. 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
  6. "Cytokinesis microtubule organisers at a glance". J Cell Sci.
  7. Yuce et al. "An ECT2–centralspindlin complex regulates the localization and function of RhoA", Journal of Cell Biology, 15 August 2005
  8. Gene Editing Rat Resource Center "Gene-Term Annotation Report", Retrieved on 01 March 2014
  9. Douglas et al. "Aurora B and 14-3-3 Coordinately Regulate Clustering of Centralspindlin during Cytokinesis", Current Biology, 25 May 2010
  10. Lee KY, Esmaeili B, Zealley B, Mishima M (2015). "Direct interaction between centralspindlin and PRC1 reinforces mechanical resilience of the central spindle". Nature Communications. 6: 7290. Bibcode:2015NatCo...6.7290L. doi:10.1038/ncomms8290. PMC 4557309. PMID 26088160.
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