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 heteroteramer consisting of two different subunit proteins:[1]
- A KIF23 dimer (Kinesin 6 motor protein, also known as MKLP1 in C. elegans)
- Consists of a motor domain linked to a parallel coiled coil and a globular region by a linker
- A RACGAP1 dimer (Also known as MgcRacGAP, KRT4 or CYK4 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 centraspindlin 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
- Interacts with RhoA and Rac during furrow ingression[4][7]
- Recruits cytokinetic effector proteins such as ECT2[6][8]
- 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[7]
- Stabilized through interactions with Aurora B kinase[9]
- Negatively regulated by 14-3-3[9]
References
- 1 2 3 4 5 6 Glotzer, Michael. "Cytokinesis: Centralspindlin Moonlights as a Membrane Anchor", Current Biology, 18 February 2013
- 1 2 3 4 5 Glotzer, Michael " The 3Ms of central spindle assembly: microtubules, motors and MAPs", Nature (Journal), January 2009
- 1 2 Nature Publishing Group. "Research Highlights", Cell Migration Consortium, 2009. Retrieved on 01 March 2014.
- 1 2 3 Lekomtsev et al. "Centralspindlin links the mitotic spindle to the plasma membrane during cytokinesis", Nature (Journal), 13 December 2012
- 1 2 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
- 1 2 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
- 1 2 Yuce et al. "An ECT2–centralspindlin complex regulates the localization and function of RhoA", Journal of Cell Biology, 15 August 2005
- ↑ Gene Editing Rat Resource Center "Gene-Term Annotation Report", Retrieved on 01 March 2014
- 1 2 Douglas et al. "Aurora B and 14-3-3 Coordinately Regulate Clustering of Centralspindlin during Cytokinesis", Current Biology, 25 May 2010