RANBP1 localizes a subset of mitotic regulatory factors on spindle microtubules and regulates chromosome segregation in human cells.
The GTPase RAN has an established role in spindle assembly and in mitotic progression, although not all mechanisms are fully understood in somatic cells. Here, we have downregulated RAN-binding protein 1 (RANBP1), a RAN partner that has highest abundance in G2 and mitosis, in human cells. RANBP1-depleted cells underwent prolonged prometaphase delay often followed by apoptosis. Cells that remained viable assembled morphologically normal spindles; these spindles, however, were hyperstable and failed to recruit cyclin B1 or to restrict the localization of HURP (DLG7), a microtubule-stabilizing factor, to plus-ends. RANBP1 depletion did not increase the frequency of unattached chromosomes; however, RANBP1-depleted cells frequently showed lagging chromosomes in anaphase, suggesting that merotelic attachments form and are not efficiently resolved. These data indicate that RANBP1 activity is required for the proper localization of specific factors that regulate microtubule function; loss of this activity contributes to the generation of aneuploidy in a microtubule-dependent manner.
Tedeschi
Antonio
A
IBPM Institute of Molecular Biology and Pathology, CNR National Research Council, Via degli Apuli 4, 00185 Rome, Italy.
Ciciarello
Marilena
M
Mangiacasale
Rosamaria
R
Roscioli
Emanuele
E
Rensen
Wilhelmina M
WM
Lavia
Patrizia
P
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D020090:Chromosome Segregation; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D034622:RNA Interference; D008941:Spindle Apparatus / Q000378:metabolism*; D020931:ran GTP-Binding Protein / Q000378:metabolism
C534699:CCNB1 protein, human; C454180:CKAP5 protein, human; D018797:Cell Cycle Proteins; D019926:Cyclin B; D056744:Cyclin B1; C465041:DLGAP5 protein, human; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C122167:TPX2 protein, human; C091775:ran-binding protein 1; D020931:ran GTP-Binding Protein