Nature Cell Biology3, 1069 - 1075 (2001)
Published online: 24 October 2001; | doi:10.1038/ncb1201-1069
A mammalian Partner of inscuteable binds NuMA and regulates mitotic spindle organization
Quansheng Du1, P. Todd Stukenberg2
& Ian G. Macara1
1
Centre for Cell Signalling and Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA
2
Department of Biochemistry, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA
Correspondence should be addressed to Quansheng Du qd2n@virginia.edu
Asymmetric cell division requires the orientation of mitotic spindles along the cell-polarity axis. In Drosophila neuroblasts, this involves the interaction of the proteins Inscuteable (Insc) and Partner of inscuteable (Pins). We report here that a human Pins-related protein, called LGN, is instead essential for the assembly and organization of the mitotic spindle. LGN is cytoplasmic in interphase cells, but associates with the spindle poles during mitosis. Ectopic expression of LGN disrupts spindle-pole organization and chromosome segregation. Silencing of LGN expression by RNA interference also disrupts spindle-pole organization and prevents normal chromosome segregation. We found that LGN binds the nuclear mitotic apparatus protein NuMA, which tethers spindles at the poles, and that this interaction is required for the LGN phenotype. Anti-LGN antibodies and the LGN-binding domain of NuMA both trigger microtubule aster formation in mitotic Xenopusegg extracts, and the NuMA-binding domain of LGN blocks aster assembly in egg extracts treated with taxol. Thus, we have identified a mammalian Pins homologue as a key regulator of spindle organization during mitosis.
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