Chromosomal Enrichment and Activation of the Aurora B Pathway Are Coupled to Spatially Regulate Spindle Assembly

• Published in: Developmental cell Vol. 12; no. 1; pp. 31 - 43
• Main Authors: Kelly, Alexander E., Sampath, Srinath C., Maniar, Tapan A., Woo, Eileen M., Chait, Brian T., Funabiki, Hironori
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 01.01.2007; Cell Press
• Subjects: Animals; Antibodies - immunology; Aurora Kinases; Biological and medical sciences; Cell differentiation, maturation, development, hematopoiesis; Cell Extracts; Cell physiology; CELLBIO; CELLCYCLE; Centrosome - metabolism; Chromosomal Proteins, Non-Histone - immunology; Chromosomal Proteins, Non-Histone - metabolism; Chromosomes - metabolism; Enzyme Activation; Fundamental and applied biological sciences. Psychology; Histones - metabolism; Microtubules - metabolism; Molecular and cellular biology; Ovum; Phosphorylation; Protein Binding; Protein Serine-Threonine Kinases - metabolism; ran GTP-Binding Protein - metabolism; Spindle Apparatus - chemistry; Spindle Apparatus - metabolism; Stathmin - metabolism; Xenopus; Xenopus - metabolism; Xenopus Proteins - immunology; Xenopus Proteins - metabolism; CELLBIO; CELLCYCLE; Development; Regulation(control); Activation
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2006.11.001

Chromatin-induced spindle assembly depends on regulation of microtubule-depolymerizing proteins by the chromosomal passenger complex (CPC), consisting of Incenp, Survivin, Dasra (Borealin), and the kinase Aurora B, but the mechanism and significance of the spatial regulation of Aurora B activity remain unclear. Here, we show that the Aurora B pathway is suppressed in the cytoplasm of Xenopus egg extract by phosphatases, but that it becomes activated by chromatin via a Ran-independent mechanism. While spindle microtubule assembly normally requires Dasra-dependent chromatin binding of the CPC, this function of Dasra can be bypassed by clustering Aurora B-Incenp by using anti-Incenp antibodies, which stimulate autoactivation among bound complexes. However, such chromatin-independent Aurora B pathway activation promotes centrosomal microtubule assembly and produces aberrant achromosomal spindle-like structures. We propose that chromosomal enrichment of the CPC results in local kinase autoactivation, a mechanism that contributes to the spatial regulation of spindle assembly and possibly to other mitotic processes.