Identification of a novel mitotic phosphorylation motif associated with protein localization to the mitotic apparatus

Yang, Feng; Camp, David G.; Gritsenko, Marina; Luo, Q.; Clauss, Therese RW; Brinkley, William R.; Smith, Richard D.; Stenoien, David L.

doi:10.1242/jcs.014795

Cited by 25 publications

(27 citation statements)

References 62 publications

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“…We repeated these experiments with GFP fused to the C terminus of Ric-8A and found that both constructs gave similar patterns of expression (data not shown). Previously, Ric-8A was identified as coprecipitating protein using a phosphorylation-specific antibody termed P190 that reacts with several members of the chromosomal passenger complex (CPC [38]). CPC proteins are known to regulate chromosomal segregation and cytokinesis (25).…”

Section: Resultsmentioning

confidence: 99%

Ric-8A and Giα Recruit LGN, NuMA, and Dynein to the Cell Cortex To Help Orient the Mitotic Spindle

Woodard

Huang

Cho

et al. 2010

Molecular and Cellular Biology

157

174

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In model organisms, resistance to inhibitors of cholinesterase 8 (Ric-8), a G protein ␣ (G␣) subunit guanine nucleotide exchange factor (GEF), functions to orient mitotic spindles during asymmetric cell divisions; however, whether Ric-8A has any role in mammalian cell division is unknown. We show here that Ric-8A and G␣ i function to orient the metaphase mitotic spindle of mammalian adherent cells. During mitosis, Ric-8A localized at the cell cortex, spindle poles, centromeres, central spindle, and midbody. Pertussis toxin proved to be a useful tool in these studies since it blocked the binding of Ric-8A to G␣ i , thus preventing its GEF activity for G␣ i . Linking Ric-8A signaling to mammalian cell division, treatment of cells with pertussis toxin, reduction of Ric-8A expression, or decreased G␣ i expression similarly affected metaphase cells. Each treatment impaired the localization of LGN (GSPM2), NuMA (microtubule binding nuclear mitotic apparatus protein), and dynein at the metaphase cell cortex and disturbed integrin-dependent mitotic spindle orientation. Live cell imaging of HeLa cells expressing green fluorescent protein-tubulin also revealed that reduced Ric-8A expression prolonged mitosis, caused occasional mitotic arrest, and decreased mitotic spindle movements. These data indicate that Ric-8A signaling leads to assembly of a cortical signaling complex that functions to orient the mitotic spindle.

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Section: Resultsmentioning

confidence: 99%

Ric-8A and Giα Recruit LGN, NuMA, and Dynein to the Cell Cortex To Help Orient the Mitotic Spindle

Woodard

Huang

Cho

et al. 2010

Molecular and Cellular Biology

157

174

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“…Recent data indicating that PR61/B'd (a PP2A subunit highly expressed in neural tissues)-null mice show neurological problems 39 highlight the importance of protein phosphatases in neural diseases. In view of the fact that phosphorylated Cdh1 is a PP2A substrate 40 , it would be very interesting to decipher whether the dysfunctional PP2A mice 39 , by impeding Cdh1 dephosphorylation during neuronal differentiation in the early embryonic period, mimic the neurodevelopmental problems observed in the Cdh1 À / À mice.…”

Section: Discussionmentioning

confidence: 99%

APC/C-Cdh1 coordinates neurogenesis and cortical size during development

et al. 2013

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The morphology of the adult brain is the result of a delicate balance between neural progenitor proliferation and the initiation of neurogenesis in the embryonic period. Here we assessed whether the anaphase-promoting complex/cyclosome (APC/C) cofactor, Cdh1-which regulates mitosis exit and G1-phase length in dividing cells-regulates neurogenesis in vivo. We use an embryo-restricted Cdh1 knockout mouse model and show that functional APC/C-Cdh1 ubiquitin ligase activity is required for both terminal differentiation of cortical neurons in vitro and neurogenesis in vivo. Further, genetic ablation of Cdh1 impairs the ability of APC/C to promote neurogenesis by delaying the exit of the progenitor cells from the cell cycle. This causes replicative stress and p53-mediated apoptotic death resulting in decreased number of cortical neurons and cortex size. These results demonstrate that APC/C-Cdh1 coordinates cortical neurogenesis and size, thus posing Cdh1 in the molecular pathogenesis of congenital neurodevelopmental disorders, such as microcephaly.

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“…5C; middle and lower panels). Finally, when we evaluated the epigenetic expression profiles in 3′-carboxyfluorescein-labeled MO- or Msk2 MO-injected embryos, we detected considerably lower expression levels of Dnmt1 and Aurkb , additional epigenetic regulators that have known mitotic functions (45,46), in Msk2 MO embryos (Fig. 5D), suggesting that Msk2 knockdown had adverse effects on other epigenetic mediators in developing embryos.…”

Section: Resultsmentioning

confidence: 94%

Comparison of epigenetic mediator expression and function in mouse and human embryonic blastomeres

Chavez

McElroy

Bossert

et al. 2014

Human Molecular Genetics

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A map of human embryo development that combines imaging, molecular, genetic and epigenetic data for comparisons to other species and across pathologies would be greatly beneficial for basic science and clinical applications. Here, we compared mRNA and protein expression of key mediators of DNA methylation and histone modifications between mouse and human embryos, embryos from fertile/infertile couples, and following growth factor supplementation. We observed that individual mouse and human embryos are characterized by similarities and distinct differences in DNA methylation and histone modification patterns especially at the single-cell level. In particular, while mouse embryos first exhibited sub-compartmentalization of different histone modifications between blastomeres at the morula stage and cell sub-populations in blastocysts, differential histone modification expression was detected between blastomeres earlier in human embryos at the four- to eight-cell stage. Likewise, differences in epigenetic mediator expression were also observed between embryos from fertile and infertile couples, which were largely equalized in response to growth factor supplementation, suggesting that select growth factors might prevent alterations in epigenetic profiles during prolonged embryo culture. Finally, we determined that reduced expression via morpholino technologies of a single histone-modifying enzyme, Rps6ka4/Msk2, resulted in cleavage-stage arrest as assessed by time-lapse imaging and was associated with aneuploidy generation. Taken together, data document differences in epigenetic patterns between species with implications for fertility and suggest functional roles for individual epigenetic factors during pre-implantation development.

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Identification of a novel mitotic phosphorylation motif associated with protein localization to the mitotic apparatus

Cited by 25 publications

References 62 publications

Ric-8A and Giα Recruit LGN, NuMA, and Dynein to the Cell Cortex To Help Orient the Mitotic Spindle

Ric-8A and Giα Recruit LGN, NuMA, and Dynein to the Cell Cortex To Help Orient the Mitotic Spindle

APC/C-Cdh1 coordinates neurogenesis and cortical size during development

Comparison of epigenetic mediator expression and function in mouse and human embryonic blastomeres

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