Centralspindlin is a motor complex implicated in cell division. It contributes to virtually every step in
cytokinesis,
[Glotzer, Michael. "Cytokinesis: Centralspindlin Moonlights as a Membrane Anchor", Current Biology, 18 February 2013] It is highly conserved in animal cells as a component of the spindle midzone and midbody.
[Glotzer, Michael " The 3Ms of central spindle assembly: microtubules, motors and MAPs", Nature, January 2009] Centralspindlin is required for the assembly of the mitotic spindle
[Nature Publishing Group. "Research Highlights", Cell Migration Consortium, 2009. Retrieved on 01 March 2014.] 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
[Lekomtsev et al. "Centralspindlin links the mitotic spindle to the plasma membrane during cytokinesis", Nature, 13 December 2012] 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:
-
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
-
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.
[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]
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.
[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]
RacGAP1 is also involved in tethering the central spindle to the plasma membrane. Without this interaction, cytokinesis cannot occur.
Interactions
