Cell and Molecular Biology of Spindle Poles and NuMA

Fant, Xavier; Merdes, Andreas; Haren, Laurence

doi:10.1016/s0074-7696(04)38001-0

Cited by 51 publications

(53 citation statements)

References 244 publications

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“…It may have as many as six microtubule-binding sites per assembled unit, and these units tend to polymerize (Harborth et al, 1999). Previous models for its function in aster and pole assembly proposed that it uses these microtubule binding sites to cross-link microtubules at the poles, perhaps acting in concert with cytoplasmic dynein (Merdes et al, 1996;Fant et al, 2004). Finding that it binds pADPr noncovalently and is also covalently modified by pADPr during mitosis (Chang et al, 2005a;Chang et al, 2005b) suggests the model in Figure 7.…”

Section: Discussionmentioning

confidence: 94%

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Interaction between Poly(ADP-ribose) and NuMA Contributes to Mitotic Spindle Pole Assembly

Chang

Coughlin

Mitchison

2009

MBoC

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Poly(ADP-ribose) (pADPr), made by PARP-5a/tankyrase-1, localizes to the poles of mitotic spindles and is required for bipolar spindle assembly, but its molecular function in the spindle is poorly understood. To investigate this, we localized pADPr at spindle poles by immuno-EM. We then developed a concentrated mitotic lysate system from HeLa cells to probe spindle pole assembly in vitro. Microtubule asters assembled in response to centrosomes and Ran-GTP in this system. Magnetic beads coated with pADPr, extended from PARP-5a, also triggered aster assembly, suggesting a functional role of the pADPr in spindle pole assembly. We found that PARP-5a is much more active in mitosis than interphase. We used mitotic PARP-5a, self-modified with pADPr chains, to capture mitosis-specific pADPr-binding proteins. Candidate binding proteins included the spindle pole protein NuMA previously shown to bind to PARP-5a directly. The rod domain of NuMA, expressed in bacteria, bound directly to pADPr. We propose that pADPr provides a dynamic cross-linking function at spindle poles by extending from covalent modification sites on PARP-5a and NuMA and binding noncovalently to NuMA and that this function helps promote assembly of exactly two poles.

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Section: Discussionmentioning

confidence: 94%

“…It is known to have asterpromoting activity in mitotic HeLa lysate (Gaglio et al, 1995) and meiotic Xenopus egg extract (Nachury et al, 2001). In cells, it is known to have minus-end focusing and spindle pole-assembly activity (Fant et al, 2004). NuMA is multimeric.…”

Section: Discussionmentioning

confidence: 99%

Interaction between Poly(ADP-ribose) and NuMA Contributes to Mitotic Spindle Pole Assembly

Chang

Coughlin

Mitchison

2009

MBoC

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“…Subsequently, components of the final MTOCs, originally scattered along the spindle axis, accumulate at spindle ends, where they organize and generate robust spindle poles (4). Our observations of aberrant spindle poles in the Δ22 NuMA mutant oocytes, together with the known function of NuMA at spindle poles in mitotic cells (reviewed in 21), prompted us to analyze the nature of these meiotic defects more closely. To do this, we followed behavior of MTOCs by immunofluorescence analysis of pericentrin, a major MTOC component, and time-lapse microscopic analysis of Venus-tagged Polo kinase 1, which has previously been shown to associate with MTOCs in meiosis (22).…”

Section: Resultsmentioning

confidence: 99%

Error-prone mammalian female meiosis from silencing the spindle assembly checkpoint without normal interkinetochore tension

Kolano

Brunet

Silk

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

140

156

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It is well established that chromosome segregation in female meiosis I (MI) is error-prone. The acentrosomal meiotic spindle poles do not have centrioles and are not anchored to the cortex via astral microtubules. By Cre recombinase-mediated removal in oocytes of the microtubule binding site of nuclear mitotic apparatus protein (NuMA), which is implicated in anchoring microtubules at poles, we determine that without functional NuMA, microtubules lose connection to MI spindle poles, resulting in highly disorganized early spindle assembly. Subsequently, very long spindles form with hyperfocused poles. The kinetochores of homologs make attachments to microtubules in these spindles but with reduced tension between them and accompanied by alignment defects. Despite this, the spindle assembly checkpoint is normally silenced and the advance to anaphase I and first polar body extrusion takes place without delay. Females without functional NuMA in oocytes are sterile, producing aneuploid eggs with altered chromosome number. These findings establish that in mammalian MI, the spindle assembly checkpoint is unable to sustain meiotic arrest in the presence of one or few misaligned and/or misattached kinetochores with reduced interkinetochore tension, thereby offering an explanation for why MI in mammals is so error-prone.

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“…NuMA is a multifunctional spindle structuring protein that has been shown to be important in bipolar spindle development and in the focusing and maintenance of MT minus ends at the poles (Fant et al, 2004;Sun and Schatten, 2006). NuMA associates with the spindle pole regions of the control spindles in the fertilized eggs (Fig.…”

Section: Mini-spindles Contain Centrosomal Materials and The Spindle Pmentioning

confidence: 99%

“…NuMA's association with the mini-spindle pole (Fig. 6) is indicative of its role in focusing the minus ends of MTs and its interaction with the dynein/dynactin complex (Fant et al, 2004;Sun and Schatten, 2006). Recent evidence suggests that NuMA may also play a key role as an overall spindle matrix protein given that it is the target of poly(ADP-ribose) addition catalyzed by the enzyme tankyrase-1 whose function is essential for mitosis .…”

Section: Mini-spindle Structural Organizationmentioning

confidence: 99%

Bipolar, anastral spindle development in artificially activated sea urchin eggs

Henson

Fried

McClellan

et al. 2008

Developmental Dynamics

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The mitotic apparatus of the early sea urchin embryo is the archetype example of a centrosome-dominated, large aster spindle organized by means of the centriole of the fertilizing sperm. In this study, we tested the hypothesis that artificially activated sea urchin eggs possess the capacity to assemble the anastral, bipolar spindles present in many acentrosomal systems. Control fertilized Lytechinus pictus embryos and ammoniaactivated eggs were immunolabeled for tubulin, centrosomal material, the spindle pole structuring protein NuMA and the mitotic kinesins MKLP1/Kinesin-6, Eg5/Kinesin-5, and KinI/Kinesin-13. Confocal imaging showed that a subset of ammonia-activated eggs contained bipolar "mini-spindles" that were anastral; displayed metaphase and anaphase-like stages; labeled for centrosomal material, NuMA, and the three mitotic kinesins; and were observed in living eggs using polarization optics. These results suggest that spindle structural and motor proteins have the ability to organize bipolar, anastral spindles in sea urchin eggs activated in the absence of the paternal centriole. Developmental Dynamics 237:1348 -1358, 2008.

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Cell and Molecular Biology of Spindle Poles and NuMA

Cited by 51 publications

References 244 publications

Interaction between Poly(ADP-ribose) and NuMA Contributes to Mitotic Spindle Pole Assembly

Interaction between Poly(ADP-ribose) and NuMA Contributes to Mitotic Spindle Pole Assembly

Error-prone mammalian female meiosis from silencing the spindle assembly checkpoint without normal interkinetochore tension

Bipolar, anastral spindle development in artificially activated sea urchin eggs

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