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Abstract
Centralspindlin, a constitutive 2:2 heterotetramer of MKLP1 (a kinesin-6) and the non-motor subunit CYK4, plays important roles in cytokinesis. It is crucial for the formation of central spindle microtubule bundle structure. Its accumulation at the central antiparallel overlap zone is key for recruitment and regulation of downstream cytokinesis factors and for stable anchoring of the plasma membrane at the midbody. Both MKLP1 and CYK4 are required for efficient microtubule bundling. However, the mechanism by which CYK4 contributes to this is unclear. Here we performed structural and functional analyses of centralspindlin using high-speed atomic force microscopy, Fӧrster resonance energy transfer analysis, and in vitro reconstitution. Our data reveal that CYK4 binds to a globular mass in the atypically long MKLP1 neck domain between the catalytic core and the coiled coil and thereby reconfigures the two motor domains in the MKLP1 dimer to be suitable for antiparallel microtubule bundling. Our work provides insights into the microtubule bundling during cytokinesis and into the working mechanisms of the kinesins with non-canonical neck structures.
Highlights
Centralspindlin is an evolutionarily conserved, constitutive 2:2 heterotetrameric complex of a kinesin-6 subunit MKLP1 and a non-motor subunit CYK4
Centralspindlin is truly central, as it organizes microtubule bundle structures, recruits other factors to the site of division, and anchors the plasma membrane at the inter-cellular bridge while the two daughter cells are waiting for the final separation
Centralspindlin is a heterotetramer composed of two molecules of a kinesin-6 motor subunit, MKLP1, and two molecules of the second subunit, CYK4
Summary
Centralspindlin is an evolutionarily conserved, constitutive 2:2 heterotetrameric complex of a kinesin-6 subunit MKLP1 and a non-motor subunit CYK4. A point mutation in KIF23/MKLP1 is the cause of congenital dyserythropoietic anemia type III, which is characterized by large multinucleated erythroblasts in bone marrow [12] Both the MKLP1 and CYK4 subunits are essential for microtubule bundling by centralspindlin [3,13]. These are included in the minimal domains of CYK-4 and ZEN-4 sufficient for in vitro reconstitution of the stable complex between them (CYK-4 1–120 and ZEN-4 435–555) These data emphasize the importance of heterotetramer formation for microtubule bundling and suggest that the tetramer assembly is achieved through compact domains without extensive contact, such as a long four-helix bundle. It remains unclear how CYK4 contributes to microtubule bundling
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