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]

  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 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

  • 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

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