MKLP1Cyk4

MKLP1Cyk4 refers to the centralspindlin complex formed by the kinesin-6 motor protein MKLP1 (KIF23) and the Rho GTPase-activating protein CYK4 (RACGAP1). This heterotetrameric complex is a key regulator of cytokinesis in animals and many eukaryotes, localizing to the central spindle (midzone) during anaphase and to the cortex at the onset of cleavage.

The centralspindlin complex functions as a microtubule-bundling and signaling hub. The MKLP1 subunit provides motor activity and microtubule binding, while CYK4 contributes a GAP domain that modulates Rho family GTPases. Centralspindlin recruits the RhoGEF ECT2 to the central spindle, promoting localized activation of RhoA at the cell cortex, which drives actomyosin contractility and cleavage furrow ingression. The complex also helps organize and stabilize microtubules at the spindle midzone, enabling proper midbody formation and successful abscission.

Structurally, MKLP1 is a kinesin-6 motor that forms dimers and associates with CYK4, yielding a functional complex that can link antiparallel microtubules. CYK4 lacks intrinsic microtubule binding but provides the GAP activity that helps regulate downstream GTPases during cytokinesis. The activity and localization of MKLP1Cyk4 are regulated by cell-cycle–dependent phosphorylation events (for example by Cdk1) and by other spindle-associated factors such as Aurora B and CEP55.

Dysfunction of MKLP1Cyk4 disrupts central spindle assembly and cytokinesis, leading to multinucleation and aneuploidy. As a conserved component of cell division, it is a focus of research into mechanisms of cytokinesis and potential targets for anti-mitotic therapies.