Chromosome- and spindle-pole-derived signals generate an intrinsic code for spindle position and orientation

Kiyomitsu, Tomomi; Cheeseman, Iain M.
March 2012
Nature Cell Biology;Mar2012, Vol. 14 Issue 3, p311
Academic Journal
Mitotic spindle positioning by cortical pulling forces defines the cell division axis and location, which is critical for proper cell division and development. Although recent work has identified developmental and extrinsic cues that regulate spindle orientation, the contribution of intrinsic signals to spindle positioning and orientation remains unclear. Here, we demonstrate that cortical force generation in human cells is controlled by distinct spindle-pole- and chromosome-derived signals that regulate cytoplasmic dynein localization. First, dynein exhibits a dynamic asymmetric cortical localization that is negatively regulated by spindle-pole proximity, resulting in spindle oscillations to centre the spindle within the cell. We find that this signal comprises the spindle-pole-localized polo-like kinase (Plk1), which regulates dynein localization by controlling the interaction between dynein-dynactin and its upstream cortical targeting factors NuMA and LGN. Second, a chromosome-derived RanGTP gradient restricts the localization of NuMA-LGN to the lateral cell cortex to define and maintain the spindle orientation axis. RanGTP acts in part through the nuclear localization sequence of NuMA to locally alter the ability of NuMA-LGN to associate with the cell cortex in the vicinity of chromosomes. We propose that these chromosome- and spindle-pole-derived gradients generate an intrinsic code to control spindle position and orientation.


Related Articles

  • Inscuteable Regulates the Pins-Mud Spindle Orientation Pathway. Mauser, Jonathon F.; Prehoda, Kenneth E. // PLoS ONE;Jan2012, Vol. 7 Issue 1, p1 

    During asymmetric cell division, alignment of the mitotic spindle with the cell polarity axis ensures that the cleavage furrow separates fate determinants into distinct daughter cells. The protein Inscuteable (Insc) is thought to link cell polarity and spindle positioning in diverse systems by...

  • The Mitotic Arrest Deficient Protein MAD2B Interacts with the Clathrin Light Chain A during Mitosis. Medendorp, Klaas; Vreede, Lilian; van Groningen, Jan J. M.; Hetterschijt, Lisette; Brugmans, Linda; Jansen, Patrick A. M.; van den Hurk, Wilhelmina H.; de Bruijn, Diederik R. H.; van Kessel, Ad Geurts // PLoS ONE;2010, Vol. 5 Issue 11, p1 

    Background: Although the mitotic arrest deficient protein MAD2B (MAD2L2) is thought to inhibit the anaphase promoting complex (APC) by binding to CDC20 and/or CDH1 (FZR1), its exact role in cell cycle control still remains to be established. Methodology/Principal Findings: Using a yeast...

  • Mitotic phosphorylation of PRC1 at Thr470 is required for PRC1 oligomerization and proper central spindle organization. Chuanhai Fu; Feng Yan; Fang Wu; Quan Wu; Whittaker, Joseph; Haiying Hu; Renming Hu; Xuebiao Yao // Cell Research;May2007, Vol. 17 Issue 5, p449 

    During cell division, chromosome segregation is orchestrated by the interaction of spindle microtubules with the centromere. A dramatic remodeling of interpolar microtubules into an organized central spindle between the separating chromatids is required for the initiation and execution of...

  • Regulation of cell cycle by the anaphase spindle midzone. Murata-Hori, Maki; Sluder, Greenfield; Yu-li Wang // BMC Cell Biology;2004, Vol. 5, p49 

    Background: A number of proteins accumulate in the spindle midzone and midbody of dividing animal cells. Besides proteins essential for cytokinesis, there are also components essential for interphase functions, suggesting that the spindle midzone and/or midbody may play a role in regulating the...

  • Multicolor Spectral Analyses of Mitotic and Meiotic Mouse Chromosomes Involved in Multiple Robertsonian Translocations. II. The NMRI/CD and CD/TA Hybrid Strains. Schmid, Michael; Steinlein, Claus; Winking, Heinz // Cytogenetic & Genome Research;Apr2017, Vol. 151 Issue 1, p18 

    Multicolor spectral analyses (spectral karyotyping) were performed on mitotic chromosomes of NMRI, CD, and TA mice and on male meiotic chromosomes (diakineses) of NMRI/CD and CD/TA hybrids. All chromosomes, including the various centric (robertsonian) fusions, could be unequivocally identified....

  • Membrane Invaginations Reveal Cortical Sites that Pull on Mitotic Spindles in One-Cell C. elegans Embryos. Redemann, Stefanie; Pecreaux, Jacques; Goehring, Nathan W.; Khairy, Khaled; Stelzer, Ernst H. K.; Hyman, Anthony A.; Howard, Jonathon // PLoS ONE;2010, Vol. 5 Issue 8, p1 

    Asymmetric positioning of the mitotic spindle in C. elegans embryos is mediated by force-generating complexes that are anchored at the plasma membrane and that pull on microtubules growing out from the spindle poles. Although asymmetric distribution of the force generators is thought to underlie...

  • Automated High-Throughput Quantification of Mitotic Spindle Positioning from DIC Movies of Caenorhabditis Embryos. Cluet, David; Stébé, Pierre-Nicolas; Riche, Soizic; Spichty, Martin; Delattre, Marie // PLoS ONE;Apr2014, Vol. 9 Issue 4, p1 

    The mitotic spindle is a microtubule-based structure that elongates to accurately segregate chromosomes during anaphase. Its position within the cell also dictates the future cell cleavage plan, thereby determining daughter cell orientation within a tissue or cell fate adoption for polarized...

  • Perturbation of Incenp function impedes anaphase chromatid movements and chromosomal passenger protein flux at centromeres. Ahonen, Leena J.; Kukkonen, Anu M.; Pouwels, Jeroen; Bolton, Margaret A.; Jingle, Christopher D.; Stukenberg, P. Todd; Kallio, Marko J. // Chromosoma;Feb2009, Vol. 118 Issue 1, p71 

    Incenp is an essential mitotic protein that, together with Aurora B, Survivin, and Borealin, forms the core of the chromosomal passenger protein complex (CPC). The CPC regulates various mitotic processes and functions to maintain genomic stability. The proper subcellular localization of the CPC...

  • Cell division: control of the chromosomal passenger complex in time and space. Horst, Armando; Lens, Susanne // Chromosoma;Mar2014, Vol. 123 Issue 1/2, p25 

    The ultimate goal of cell division is equal transmission of the duplicated genome to two new daughter cells. Multiple surveillance systems exist that monitor proper execution of the cell division program and as such ensure stability of our genome. One widely studied protein complex essential for...

  • Cell Cycle.  // Encyclopedic Reference of Cancer;2001, p187 

    A definition of the term "cell cycle" is presented. It is more correctly known as cell division cycle and it is a highly ordered series of stages through which a cell progresses in order to duplicate its chromosomes and divide. It mentions that the four phases of cell cycle are Gap 1, DNA...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics