An Inner Centromere Protein that Stimulates the Microtubule Depolymerizing Activity of a KinI Kinesin

• Published in: Developmental cell Vol. 5; no. 2; pp. 309 - 321
• Main Authors: Ohi, Ryoma, Coughlin, Margaret L, Lane, William S, Mitchison, Timothy J
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2003
• Subjects: Amino Acid Sequence; Animals; Aurora Kinase B; Aurora Kinases; Cell Cycle Proteins - metabolism; Cell Line; Centromere - chemistry; Centromere - metabolism; Centromere - ultrastructure; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; Humans; Kinesin - genetics; Kinesin - metabolism; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Microtubules - metabolism; Mitosis - physiology; Molecular Sequence Data; Oocytes - physiology; Protein-Serine-Threonine Kinases - metabolism; S-Phase Kinase-Associated Proteins; Sequence Alignment; Spindle Apparatus - metabolism; Tissue Extracts; Xenopus; Xenopus laevis; Xenopus Proteins - genetics; Xenopus Proteins - metabolism
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/S1534-5807(03)00229-6

Mitosis requires precise control of microtubule dynamics. The KinI kinesin MCAK, a microtubule depolymerase, is critical for this regulation. In a screen to discover previously uncharacterized microtubule-associated proteins, we identified ICIS, a protein that stimulates MCAK activity in vitro. Consistent with this biochemical property, blocking ICIS function in Xenopus extracts with antibodies caused excessive microtubule growth and inhibited spindle formation. Prior to anaphase, ICIS localized in an MCAK-dependent manner to inner centromeres, the chromosomal region located in between sister kinetochores. From Xenopus extracts, ICIS coimmunoprecipitated MCAK and the inner centromere proteins INCENP and Aurora B, which are thought to promote chromosome biorientation. By immunoelectron microscopy, we found that ICIS is present on the surface of inner centromeres, placing it in an ideal location to depolymerize microtubules associated laterally with inner centromeres. At inner centromeres, MCAK-ICIS may destabilize these microtubules and provide a mechanism that prevents kinetochore-microtubule attachment errors.