Midzone activation of aurora B in anaphase produces an intracellular phosphorylation gradient.
ABSTRACT Proper partitioning of the contents of a cell between two daughters requires integration of spatial and temporal cues. The anaphase array of microtubules that self-organize at the spindle midzone contributes to positioning the cell-division plane midway between the segregating chromosomes. How this signalling occurs over length scales of micrometres, from the midzone to the cell cortex, is not known. Here we examine the anaphase dynamics of protein phosphorylation by aurora B kinase, a key mitotic regulator, using fluorescence resonance energy transfer (FRET)-based sensors in living HeLa cells and immunofluorescence of native aurora B substrates. Quantitative analysis of phosphorylation dynamics, using chromosome- and centromere-targeted sensors, reveals that changes are due primarily to position along the division axis rather than time. These dynamics result in the formation of a spatial phosphorylation gradient early in anaphase that is centred at the spindle midzone. This gradient depends on aurora B targeting to a subpopulation of microtubules that activate it. Aurora kinase activity organizes the targeted microtubules to generate a structure-based feedback loop. We propose that feedback between aurora B kinase activation and midzone microtubules generates a gradient of post-translational marks that provides spatial information for events in anaphase and cytokinesis.
Cell cycle (Georgetown, Tex.) 10/2014; 13(19):2985-2986. DOI:10.4161/15384101.2014.959853 · 5.01 Impact Factor
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ABSTRACT: Here we discuss a "chromosome separation checkpoint" that might regulate the anaphase-telophase transition. The concept of cell cycle checkpoints was originally proposed to account for extrinsic control mechanisms that ensure the order of cell cycle events. Several checkpoints have been shown to regulate major cell cycle transitions, namely at G1-S and G2-M. At the onset of mitosis, the prophase-prometaphase transition is controlled by several potential checkpoints, including the antephase checkpoint, while the spindle assembly checkpoint guards the metaphase-anaphase transition. Our hypothesis is based on the recently uncovered feedback control mechanism that delays chromosome decondensation and nuclear envelope reassembly until effective separation of sister chromatids during anaphase is achieved. A central player in this potential checkpoint is the establishment of a constitutive, midzone-based Aurora B phosphorylation gradient that monitors the position of chromosomes along the spindle axis. We propose that this surveillance mechanism represents an additional step towards ensuring mitotic fidelity. © 2014 WILEY Periodicals, Inc.BioEssays 12/2014; DOI:10.1002/bies.201400140 · 4.84 Impact Factor
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ABSTRACT: The mitotic spindle is the macromolecular machine utilized to accurately segregate chromosomes in cells. How this self-organized structure assembles is a key aspect of understanding spindle morphogenesis. In the present review, we focus on understanding mechanisms of spindle self-assembly and address how subcellular signalling gradients, such as Ran-GTP and Aurora B, contribute to spindle organization and function.Biochemical Society Transactions 02/2015; 43(1):7-12. DOI:10.1042/BST20140243 · 3.24 Impact Factor