Nature Cell Biology 8, 586 - 593 (2006)
Published online: 30 April 2006; | doi:10.1038/ncb1409
Drosophila Pins-binding protein Mud regulates spindle-polarity coupling and centrosome organizationYasushi Izumi1, Nao Ohta1, Kanako Hisata1, Thomas Raabe2
& Fumio Matsuzaki11
Laboratory for Cell Asymmetry, Center for Developmental Biology, RIKEN, and CREST, Japan Science and Technology Corporation, 2-2-3 Minatojima-Minamimachi, Chuou-ku, Kobe 650-0047, Japan. 2
Institute for Medical Radiation and Cell Research, University of Wuerzburg, Versbacherstr. 5, 97078 Wuerzburg, Germany.
Correspondence should be addressed to Yasushi Izumi izumi@cdb.riken.jp or Fumio Matsuzaki fumio@cdb.riken.jp PinsMudNuMALin-5aPKCPar-3Par-6G iThe orientation of the mitotic spindle relative to the cell axis determines whether polarized cells undergo symmetric or asymmetric divisions. Drosophila epithelial cells and neuroblasts provide an ideal pair of cells to study the regulatory mechanisms involved. Epithelial cells divide symmetrically, perpendicular to the apical–basal axis. In the asymmetric divisions of neuroblasts, by contrast, the spindle reorients parallel to that axis, leading to the unequal distribution of cell-fate determinants to one daughter cell1. Receptor-independent G-protein signalling involving the GoLoco protein Pins is essential for spindle orientation in both cell types2. Here, we identify Mushroom body defect (Mud)3 as a downstream effector in this pathway. Mud directly associates and colocalizes with Pins at the cell cortex overlying the spindle pole(s) in both neuroblasts and epithelial cells. The cortical Mud protein is essential for proper spindle orientation in the two different division modes. Moreover, Mud localizes to centrosomes during mitosis independently of Pins to regulate centrosomal organization. We propose that Drosophila Mud, vertebrate NuMA
4 and Caenorhabditis elegans Lin-5 (refs 5, 6) have conserved roles in the mechanism by which G-proteins regulate the mitotic spindle.
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