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]