Nuclei of Non-Muscle Cells Bind Centrosome Proteins upon Fusion with Differentiating Myoblasts

Fant, Xavier; Sršeň, Vlastimil; Espigat-Georger, Aude; Merdes, Andreas

doi:10.1371/journal.pone.0008303

Cited by 31 publications

(34 citation statements)

References 21 publications

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“…The rapid cell cycles in the developing embryo did not allow us to test whether increased incubation would result in mitotic events such as chromosome condensation or nuclear envelope breakdown that is predicted from classic cell fusion experiments [18]. Interestingly, a previous report found that the nuclear MTOC state of a muscle cell can convert the centrosome MTOC state of a U2OS cell, suggesting that, in some contexts, a non-centrosomal MTOC state can be dominant [28]. By combining photobleaching with cell fusion, we found that the SPD-2 adding onto the centrosome in the interphase cell following fusion conversion came only from the mitotic cell.…”

Section: Discussionmentioning

confidence: 98%

SPD-2/CEP192 and CDK Are Limiting for Microtubule-Organizing Center Function at the Centrosome

Yang

Feldman

2015

Current Biology

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The centrosome acts as the microtubule-organizing center (MTOC) during mitosis in animal cells. Microtubules are nucleated and anchored by γ-tubulin ring complexes (γ-TuRCs) embedded within the centrosome's pericentriolar material (PCM). The PCM is required for the localization of γ-TuRCs, and both are steadily recruited to the centrosome, culminating in a peak in MTOC function in metaphase. In differentiated cells, the centrosome is often attenuated as an MTOC and MTOC function is reassigned to non-centrosomal sites such as the apical membrane in epithelial cells, the nuclear envelope in skeletal muscle, and down the lengths of axons and dendrites in neurons. Hyperactive MTOC function at the centrosome is associated with epithelial cancers and with invasive behavior in tumor cells. Little is known about the mechanisms that limit MTOC activation at the centrosome. Here, we find that MTOC function at the centrosome is completely inactivated during cell differentiation in C. elegans embryonic intestinal cells and MTOC function is reassigned to the apical membrane. In cells that divide after differentiation, the cellular MTOC state switches between the membrane and the centrosome. Using cell fusion experiments in live embryos, we find that the centrosome MTOC state is dominant and that the inactive MTOC state of the centrosome is malleable; fusion of a mitotic cell to a differentiated or interphase cell results in rapid reactivation of the centrosome MTOC. We show that conversion of MTOC state involves the conserved centrosome protein SPD-2/CEP192 and CDK activity from the mitotic cell.

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Section: Discussionmentioning

confidence: 98%

SPD-2/CEP192 and CDK Are Limiting for Microtubule-Organizing Center Function at the Centrosome

Yang

Feldman

2015

Current Biology

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“…The dependence of myonuclear distribution on microtubules was originally inferred from pharmacological experiments and from correlative studies of nuclear position and the microtubule network (Englander and Rubin, 1987;Bruusgaard et al, 2006), and has more recently been shown by Cadot et al (2012) and Metzger et al (2012). Initial formation of microtubule filaments in myotubes might involve microtubule-nucleating activity on the nuclear surface (Tassin et al, 1985a;Bugnard et al, 2005;Fant et al, 2009). However, microtubules in our early differentiated C2C12 cultures were mostly seen in a parallel orientation along the length of the cell, with long microtubules running past nuclei instead of attaching end-on to their nuclear surface (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, nesprins and related proteins have been shown to interact with components of the microtubule network, such as kinesin, dynein and dynactin, and with the centrosome (Malone et al, 2003;Roux et al, 2009;Zhang et al, 2009;Zhou et al, 2009;Fridolfsson et al, 2010;Yu et al, 2011;Holzbaur, 2012, 2015). Several groups have reported that proteins of the centrosome, such as PCM-1, pericentrin and γ-tubulin, are relocated from the pericentriolar material to the nuclear envelope upon onset of myoblast differentiation, and that a substantial amount of microtubules grow from the nuclear surface following this reorganization (Tassin et al, 1985a;Bugnard et al, 2005;Srsen et al, 2009;Fant et al, 2009). In this study, we show that nesprin-1 is essential for the relocalization of centrosome proteins and components of microtubule motor complexes to the nuclear envelope in differentiating mouse myoblasts, and that nesprin-1 and the centrosome protein PCM-1 are needed for regular positioning of nuclei in these cells.…”

Section: Introductionmentioning

confidence: 99%

Nuclear alignment in myotubes requires centrosome proteins recruited by nesprin-1

Espigat-Georger

Dyachuk

Chemin

et al. 2016

Journal of Cell Science

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Myotubes are syncytial cells generated by fusion of myoblasts. Among the numerous nuclei in myotubes of skeletal muscle fibres, the majority are equidistantly positioned at the periphery, except for clusters of multiple nuclei underneath the motor endplate. The correct positioning of nuclei is thought to be important for muscle function and requires nesprin-1 (also known as SYNE1), a protein of the nuclear envelope. Consistent with this, mice lacking functional nesprin-1 show defective nuclear positioning and present aspects of Emery-Dreifuss muscular dystrophy. In this study, we perform small interfering RNA (siRNA) experiments in C2C12 myoblasts undergoing differentiation, demonstrating that the positioning of nuclei requires PCM-1, a protein of the centrosome that relocalizes to the nuclear envelope at the onset of differentiation in a manner that is dependent on the presence of nesprin-1. PCM-1 itself is required for recruiting proteins of the dynein-dynactin complex and of kinesin motor complexes. This suggests that microtubule motors that are attached to the nuclear envelope support the movement of nuclei along microtubules, to ensure their correct positioning in the myotube.

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“…Required for stability of the cTuSC subunits c-tubulin, GCP2 and GCP3 (Fant et al, 2009b) Keratin Binds directly to GCP6 and assembles c-tubulin-containing nucleation sites in the apical domain of epithelial cells; interaction with GCP6 is disrupted by CDK1-dependent GCP6 phosphorylation (Oriolo et al, 2007) Augmin complex Enhanced interaction with cTuRC during mitosis; recruits cTuRC to spindle microtubules through GCP-WD to promote intra-spindle microtubule generation (Goshima et al, 2008;Lawo et al, 2009;Uehara et al, 2009;Zhu et al, 2008) …”

Section: Hca66mentioning

confidence: 99%

The where, when and how of microtubule nucleation – one ring to rule them all

Teixidó-Travesa¹,

Roig

Lüders³

2012

Journal of Cell Science

153

162

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SummaryThe function of microtubules depends on their arrangement into highly ordered arrays. Spatio-temporal control over the formation of new microtubules and regulation of their properties are central to the organization of these arrays. The nucleation of new microtubules requires c-tubulin, an essential protein that assembles into multi-subunit complexes and is found in all eukaryotic organisms. However, the way in which c-tubulin complexes are regulated and how this affects nucleation and, potentially, microtubule behavior, is poorly understood. c-tubulin has been found in complexes of various sizes but several lines of evidence suggest that only large, ring-shaped complexes function as efficient microtubule nucleators. Human c-tubulin ring complexes (cTuRCs) are composed of c-tubulin and the c-tubulin complex components (GCPs) 2, 3, 4, 5 and 6, which are members of a conserved protein family. Recent work has identified additional unrelated cTuRC subunits, as well as a large number of more transient cTuRC interactors. In this Commentary, we discuss the regulation of cTuRC-dependent microtubule nucleation as a key mechanism of microtubule organization. Specifically, we focus on the regulatory roles of the cTuRC subunits and interactors and present an overview of other mechanisms that regulate cTuRC-dependent microtubule nucleation and organization.

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Nuclei of Non-Muscle Cells Bind Centrosome Proteins upon Fusion with Differentiating Myoblasts

Cited by 31 publications

References 21 publications

SPD-2/CEP192 and CDK Are Limiting for Microtubule-Organizing Center Function at the Centrosome

SPD-2/CEP192 and CDK Are Limiting for Microtubule-Organizing Center Function at the Centrosome

Nuclear alignment in myotubes requires centrosome proteins recruited by nesprin-1

The where, when and how of microtubule nucleation – one ring to rule them all

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