NuMA after 30 years: the matrix revisited

Radulescu, Andreea E.; Cleveland, Don W.

doi:10.1016/j.tcb.2010.01.003

Cited by 153 publications

(164 citation statements)

References 89 publications

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“…Similarly, NuMA was recruited to ablation-created minus-ends when dynein was inhibited by p150-CC1 over-expression (Figure 2-figure supplement 1A,B). Thus, NuMA localizes to minus-ends without dynein carrying it there -consistent with early observations in extract asters and spindles (Gaglio et al, 1996;Heald et al, 1997) but in contrast to the prevailing view that dynein delivers NuMA to minus-ends (Merdes et al, 2000;Radulescu and Cleveland, 2010). Slower NuMA accumulation kinetics after p50 overexpression suggest that dynein-dynactin-NuMA complex formation may aid rapid NuMA recruitment, but dynein 'Walk and Pile-up' alone cannot explain NuMA's minus-end affinity ( Figure 2D,E).…”

Section: Numa Localizes To Minus-ends Independently Of Dyneinsupporting

confidence: 87%

NuMA Recruits Dynein Activity to Microtubule Minus-Ends at Mitosis

Hueschen

Kenny

et al. 2018

Biophysical Journal

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To build the spindle at mitosis, motors exert spatially regulated forces on microtubules. We know that dynein pulls on mammalian spindle microtubule minus-ends, and this localized activity at ends is predicted to allow dynein to cluster microtubules into poles. How dynein becomes enriched at minus-ends is not known. Here, we use quantitative imaging and laser ablation to show that NuMA targets dynactin to minus-ends, localizing dynein activity there. NuMA is recruited to new minus-ends independently of dynein and more quickly than dynactin; both NuMA and dynactin display specific, steady-state binding at minus-ends. NuMA localization to minus-ends involves a C-terminal region outside NuMA's canonical microtubule-binding domain and is independent of minus-end binders g-TuRC, CAMSAP1, and KANSL1/3. Both NuMA's minus-endbinding and dynein-dynactin-binding modules are required to rescue focused, bipolar spindle organization. Thus, NuMA may serve as a mitosis-specific minus-end cargo adaptor, targeting dynein activity to minus-ends to cluster spindle microtubules into poles.

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Section: Numa Localizes To Minus-ends Independently Of Dyneinsupporting

confidence: 87%

NuMA Recruits Dynein Activity to Microtubule Minus-Ends at Mitosis

Hueschen

Kenny

et al. 2018

Biophysical Journal

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“…We first addressed whether NuMA (Nuclear Mitotic Apparatus protein) (14)(15)(16)(17)(18)(19), one of the conserved polar proteins, is localized to the cell cortex as well as spindle poles during cell division by using HeLa cells as a control (16). Immunostaining experiments showed that NuMA is localized to the nucleus during interphase, as reported previously (15), and to spindle poles throughout mitosis (Fig.…”

Section: Acd Preferentially Occurs In Human Neuroblastoma Cells With Asupporting

confidence: 64%

Evidence of asymmetric cell division and centrosome inheritance in human neuroblastoma cells

Izumi

Kaneko

2012

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

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Asymmetric cell division (ACD) is believed to be a physiological event that occurs during development and tissue homeostasis in a large variety of organisms. ACD produces two unequal daughter cells, one of which resembles a multipotent stem and/or progenitor cell, whereas the other has potential for differentiation. Although recent studies have shown that the balance between self-renewal and differentiation potentials is precisely controlled and that alterations in the balance may lead to tumorigenesis in Drosophila neuroblasts, it is largely unknown whether human cancer cells directly show ACD in an evolutionarily conserved manner. Here, we show that the conserved polarity/spindle protein NuMA is preferentially localized to one side of the cell cortex during cell division, generating unequal inheritance of fate-altering molecules in human neuroblastoma cell lines. We also show that the cells with a single copy of MYCN showed significantly higher percentages of ACD than those with MYCN amplification. Moreover, suppression of MYCN in MYCN-amplified cells caused ACD, whereas expression of MYCN in MYCN-nonamplified cells enhanced symmetric cell division. Furthermore, we demonstrate that centrosome inheritance follows a definite rule in ACD: The daughter centrosome with younger mother centriole is inherited to the daughter cell with NuMA preferentially localized to the cell cortex, whereas the mother centrosome with the older mother centriole migrates to the other daughter cell. Thus, the mechanisms of cell division of ACD or symmetric cell division and centrosome inheritance are recapitulated in human cancer cells, and these findings may facilitate studies on cancer stem cells.

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“…32 Furthermore, a recent study in C. elegans established a role for CDK-1 as an inhibitor of meiotic spindle rotation and proposed a model in which Cdk-1 inhibits cytoplasmic dynein activity by preventing its interaction with LIN-5, a NuMA ortholog. 33 While the preferred localization of a subset of NuMA to the meiotic spindle attached to the animal cortex is unknown, our results identify Cdc6 as the first molecular marker that displays such asymmetric pole localization at the time of spindle rotation and attachment to the oocyte's animal cortex.…”

Section: Discussionmentioning

confidence: 99%