A Unique Set of Centrosome Proteins Requires Pericentrin for Spindle-Pole Localization and Spindle Orientation

Chen, Chun‐Ting; Hehnly, Heidi; Qian, Yu; Farkas, Debby; Ge, Zheng; Redick, Sambra D.; Hung, Hui-Fang; Samtani, Rajeev; Jurczyk, Agata; Akbarian, Schahram; Wise, Carol A.; Jackson, Andrew P.; Bober, Michael B.; Yin, Guisheng; Lo, Cecilia; Doxsey, Stephen

doi:10.1016/j.cub.2014.11.037

Cited by 25 publications

(44 citation statements)

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“…Our findings also indicate that Pcnt is required for the recruitment of Cep215 (Cdk5Rap2), the homolog of Drosophila Cnn (Kim and Rhee, 2014), to aMTOCs. Cep215 together with ninein and centriolin were identified as a subset of key proteins that are targeted to mitotic spindle poles by Pcnt, and play an important role in MT anchoring as well as the formation of mature spindle poles in somatic cells (Chen et al, 2014). Loss of this complex in Pcnt −/− embryonic fibroblasts disrupts astral MT formation and attachment to the cell cortex, leading to significant spindle misorientation (Chen et al, 2014).…”

Section: Loss Of Pcnt Disrupts Amtoc-associated Proteinsmentioning

confidence: 99%

“…Cep215 together with ninein and centriolin were identified as a subset of key proteins that are targeted to mitotic spindle poles by Pcnt, and play an important role in MT anchoring as well as the formation of mature spindle poles in somatic cells (Chen et al, 2014). Loss of this complex in Pcnt −/− embryonic fibroblasts disrupts astral MT formation and attachment to the cell cortex, leading to significant spindle misorientation (Chen et al, 2014). In contrast, Pcnt-depleted oocytes show no overt defects in spindle orientation and polar body formation, as the meiotic spindle is normally devoid of astral MTs and spindle positioning is instead dependent on the actin network (Azoury et al, 2008;Leader et al, 2002).…”

Section: Loss Of Pcnt Disrupts Amtoc-associated Proteinsmentioning

confidence: 99%

“…Loss-of-function mutations in the human Pcnt gene (PCNT) are causally linked to a rare and severe form of primordial dwarfism (MOPDII), further supporting its central role in cell division (Griffith et al, 2008;Rauch et al, 2008). Pcnt −/− mice show a similar pathology to MOPDII with significant in utero growth restriction and developmental defects that can lead to embryonic lethality (Chen et al, 2014). Pcnt is expressed in mouse oocytes, where it localizes specifically to aMTOCs during oocyte growth and throughout the progression of meiotic division (Łuksza et al, 2013;Ma and Viveiros, 2014;Schuh and Ellenberg, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Error-prone meiotic division and subfertility in mice with oocyte-conditional knockdown of pericentrin

Baumann

Wang

Yang

et al. 2017

Journal of Cell Science

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Mouse oocytes lack canonical centrosomes and instead contain unique acentriolar microtubule-organizing centers (aMTOCs). To test the function of these distinct aMTOCs in meiotic spindle formation, pericentrin (Pcnt), an essential centrosome/MTOC protein, was knocked down exclusively in oocytes by using a transgenic RNAi approach. Here, we provide evidence that disruption of aMTOC function in oocytes promotes spindle instability and severe meiotic errors that lead to pronounced female subfertility. Pcnt-depleted oocytes from transgenic (Tg) mice were ovulated at the metaphase-II stage, but show significant chromosome misalignment, aneuploidy and premature sister chromatid separation. These defects were associated with loss of key Pcnt-interacting proteins (γ-tubulin, Nedd1 and Cep215) from meiotic spindle poles, altered spindle structure and chromosome-microtubule attachment errors. Live-cell imaging revealed disruptions in the dynamics of spindle assembly and organization, together with chromosome attachment and congression defects. Notably, spindle formation was dependent on Ran GTPase activity in Pcnt-deficient oocytes. Our findings establish that meiotic division is highly error-prone in the absence of Pcnt and disrupted aMTOCs, similar to what reportedly occurs in human oocytes. Moreover, these data underscore crucial differences between MTOC-dependent and -independent meiotic spindle assembly.

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Section: Loss Of Pcnt Disrupts Amtoc-associated Proteinsmentioning

confidence: 99%

Section: Loss Of Pcnt Disrupts Amtoc-associated Proteinsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Error-prone meiotic division and subfertility in mice with oocyte-conditional knockdown of pericentrin

Baumann

Wang

Yang

et al. 2017

Journal of Cell Science

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“…It was recently reported that centriolin depletion displaces the centrosomal components 22 and misoriented spindles are associated with loss of a unique set of centrosome proteins (ninein, Cep215, and centriolin) from the spindle poles. 10 However, how depletion of centriolin in meiotic oocytes leads to failure of asymmetric division requires further study.…”

Section: Discussionmentioning

confidence: 99%

“…9 Mis-oriented spindles were also found to be associated with disrupted astral microtubules and the loss of a unique set of centrosome proteins from the spindle poles, including ninein, Cep215, and centriolin. 10 This study aimed to clarify whether centriolin, as a centrioleappendage protein, regulates the progression of oocyte meiotic maturation, focusing on meiotic spindle organization, cytokinesis, and asymmetric division.…”

Section: Introductionmentioning

confidence: 99%

Centriolin, a centriole-appendage protein, regulates peripheral spindle migration and asymmetric division in mouse meiotic oocytes

et al. 2017

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Unlike somatic cells mitosis, germ cell meiosis consists of 2 consecutive rounds of division that segregate homologous chromosomes and sister chromatids, respectively. The meiotic oocyte is characterized by an absence of centrioles and asymmetric division. Centriolin is a relatively novel centriolar protein that functions in mitotic cell cycle progression and cytokinesis. Here, we explored the function of centriolin in meiosis and showed that it is localized to meiotic spindles and concentrated at the spindle poles and midbody during oocyte meiotic maturation. Unexpectedly, knockdown of centriolin in oocytes with either siRNA or Morpholino micro-injection, did not affect meiotic spindle organization, cell cycle progression, or cytokinesis (as indicated by polar body emission), but led to a failure of peripheral meiotic spindle migration, large polar body emission, and 2-cell like oocytes. These data suggest that, unlike in mitotic cells, the centriolar protein centriolin does not regulate cytokinesis, but plays an important role in regulating asymmetric division of meiotic oocytes.

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New dimensions of asymmetric division in vertebrates

et al. 2018

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Traditionally, we imagine that cell division gives rise to two identical daughter cells. Nevertheless, all cell divisions, to some degree, display asymmetry. Asymmetric cell division is defined as the generation of two daughter cells with different physical content and/or developmental potential. Several organelles and cellular components including the centrosome, non-coding RNA, chromatin, and recycling endosomes are involved in the process of asymmetric cell division. Disruption of this important process is known to induce profound defects in development, the immune response, regeneration of tissues, aging, and cancer. Here, we discuss recent advances that expand our understanding of the mechanisms and consequences of asymmetric cell division in vertebrate organisms.

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A Unique Set of Centrosome Proteins Requires Pericentrin for Spindle-Pole Localization and Spindle Orientation

Cited by 25 publications

References 0 publications

Error-prone meiotic division and subfertility in mice with oocyte-conditional knockdown of pericentrin

Error-prone meiotic division and subfertility in mice with oocyte-conditional knockdown of pericentrin

Centriolin, a centriole-appendage protein, regulates peripheral spindle migration and asymmetric division in mouse meiotic oocytes

New dimensions of asymmetric division in vertebrates

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