The Drosophila NuMA Homolog Mud regulates spindle orientation in asymmetric cell division.
During asymmetric cell division, the mitotic spindle must be properly oriented to ensure the asymmetric segregation of cell fate determinants into only one of the two daughter cells. In Drosophila neuroblasts, spindle orientation requires heterotrimeric G proteins and the G alpha binding partner Pins, but how the Pins-G alphai complex interacts with the mitotic spindle is unclear. Here, we show that Pins binds directly to the microtubule binding protein Mud, the Drosophila homolog of NuMA. Like NuMA, Mud can bind to microtubules and enhance microtubule polymerization. In the absence of Mud, mitotic spindles in Drosophila neuroblasts fail to align with the polarity axis. This can lead to symmetric segregation of the cell fate determinants Brat and Prospero, resulting in the mis-specification of daughter cell fates and tumor-like over proliferation in the Drosophila nervous system. Our data suggest a model in which asymmetrically localized Pins-G alphai complexes regulate spindle orientation by directly binding to Mud.
Bowman
Sarah K
SK
Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr. Bohr Gasse 3-5, 1030 Vienna, Austria.
Neumüller
Ralph A
RA
Novatchkova
Maria
M
Du
Quansheng
Q
Knoblich
Juergen A
JA
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D034961:Antigens, Nuclear / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D001665:Binding Sites; D018797:Cell Cycle Proteins; D002455:Cell Division; D016764:Cell Polarity; D017124:Conserved Sequence; D004330:Drosophila / Q000166:cytology / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004625:Embryo, Nonmammalian; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000737:chemistry / Q000378:metabolism; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D034521:Nuclear Matrix-Associated Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D010802:Phylogeny; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D008941:Spindle Apparatus / Q000502:physiology*
D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D020730:Guanine Nucleotide Dissociation Inhibitors; D019476:Insect Proteins; D008565:Membrane Proteins; C411670:Mud protein, Drosophila; C050045:NUMA1 protein, human; D009419:Nerve Tissue Proteins; D034521:Nuclear Matrix-Associated Proteins; C405164:Pins protein, Drosophila; D019206:GTP-Binding Protein alpha Subunits, Gi-Go