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Spatiotemporal control of mitosis by the conserved spindle matrix protein Megator
Authors:Mariana Lince-Faria  Stefano Maffini  Bernard Orr  Yun Ding  Cláudia Florindo  Claudio E Sunkel  álvaro Tavares  J?rgen Johansen  Kristen M Johansen  Helder Maiato
Institution:1.Instituto de Biologia Molecular e Celular, 2.Instituto de Ciências Biomédicas de Abel Salazar, and 3.Laboratory for Cell and Molecular Biology, Faculdade de Medicina, Universidade do Porto, 4150-180 Porto, Portugal;4.Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, IA 50011;5.Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal
Abstract:A putative spindle matrix has been hypothesized to mediate chromosome motion, but its existence and functionality remain controversial. In this report, we show that Megator (Mtor), the Drosophila melanogaster counterpart of the human nuclear pore complex protein translocated promoter region (Tpr), and the spindle assembly checkpoint (SAC) protein Mad2 form a conserved complex that localizes to a nuclear derived spindle matrix in living cells. Fluorescence recovery after photobleaching experiments supports that Mtor is retained around spindle microtubules, where it shows distinct dynamic properties. Mtor/Tpr promotes the recruitment of Mad2 and Mps1 but not Mad1 to unattached kinetochores (KTs), mediating normal mitotic duration and SAC response. At anaphase, Mtor plays a role in spindle elongation, thereby affecting normal chromosome movement. We propose that Mtor/Tpr functions as a spatial regulator of the SAC, which ensures the efficient recruitment of Mad2 to unattached KTs at the onset of mitosis and proper spindle maturation, whereas enrichment of Mad2 in a spindle matrix helps confine the action of a diffusible “wait anaphase” signal to the vicinity of the spindle.
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