title: Drosophila Pins-binding protein Mud regulates spindle-polarity coupling and centrosome organization.
abstract: The 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 cell. Receptor-independent G-protein signalling involving the GoLoco protein Pins is essential for spindle orientation in both cell types. Here, we identify Mushroom body defect (Mud) 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 and Caenorhabditis elegans Lin-5 (refs 5, 6) have conserved roles in the mechanism by which G-proteins regulate the mitotic spindle.
authors.affiliation: 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. izumi@cdb.riken.jp
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Izumi
authors.forename: Nao
authors.initials: N
authors.lastname: Ohta
authors.forename: Kanako
authors.initials: K
authors.lastname: Hisata
authors.forename: Thomas
authors.initials: T
authors.lastname: Raabe
authors.forename: Fumio
authors.initials: F
authors.lastname: Matsuzaki
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins; D016764:Cell Polarity; D018385:Centrosome; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism* / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology; D019204:GTP-Binding Proteins / Q000502:physiology; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000166:cytology; D011485:Protein Binding; D008941:Spindle Apparatus
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D020730:Guanine Nucleotide Dissociation Inhibitors; D008565:Membrane Proteins; C411670:Mud protein, Drosophila; D009419:Nerve Tissue Proteins; C405164:Pins protein, Drosophila; D019204:GTP-Binding Proteins