title: Rab5 GTPase controls chromosome alignment through Lamin disassembly and relocation of the NuMA-like protein Mud to the poles during mitosis.
abstract: The small GTPase Rab5 is a conserved regulator of membrane trafficking; it regulates the formation of early endosomes, their transport along microtubules, and the fusion to the target organelles. Although several members of the endocytic pathway were recently implicated in spindle organization, it is unclear whether Rab5 has any role during mitosis. Here, we describe that Rab5 is required for proper chromosome alignment during Drosophila mitoses. We also found that Rab5 associated in vivo with nuclear Lamin and mushroom body defect (Mud), the Drosophila counterpart of nuclear mitotic apparatus protein (NuMA). Consistent with this finding, Rab5 was required for the disassembly of the nuclear envelope at mitotic entry and the accumulation of Mud at the spindle poles. Furthermore, Mud depletion caused chromosome misalignment defects that resembled the defects of Rab5 RNAi cells, and double-knockdown experiments indicated that the two proteins function in a linear pathway. Our results indicate a role for Rab5 in mitosis and reinforce the emerging view of the contributions made by cell membrane dynamics to spindle function.
authors: Cancer Research United Kingdom Cell Cycle Genetics Research Group, Department of Genetics, University of Cambridge, Cambridge CB2 3EH, United Kingdom. lc284@cam.ac.uk
authors: Luisa
authors: L
authors: Capalbo
authors: Pier Paolo
authors: PP
authors: D'Avino
authors: Vincent
authors: V
authors: Archambault
authors: David M
authors: DM
authors: Glover
mesh_terms: D000818:Animals; D002460:Cell Line; D020090:Chromosome Segregation / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism; D034882:Lamins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism; D020696:rab5 GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; C440328:Lam protein, Drosophila; D034882:Lamins; D008565:Membrane Proteins; C411670:Mud protein, Drosophila; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; C072004:polo protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D020696:rab5 GTP-Binding Proteins