ArticleNature cell biology2011
aPKC phosphorylates NuMA-related LIN-5 to position the mitotic spindle during asymmetric division.
Article in Nature cell biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 70 citations in OpenAlex.
- Quantitative perturbation-phenotype maps reveal nonlinear responses underlying robustness of PAR-dependent asymmetric cell division.PLoS biology · 2024Article
- A cytokinetic ring-driven cell rotation achieves Hertwig's rule in early development.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Apical PAR protein caps orient the mitotic spindle in C. elegans early embryos.Current biology : CB · 2023Article
- Apical PAR-3 caps orient the mitotic spindle inbioRxiv : the preprint server for biology · 2023Article
- The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Review
- Going with the flow: insights fromPhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2020Review
- Polar relaxation by dynein-mediated removal of cortical myosin II.The Journal of cell biology · 2020Article
- Article
- Dysfunctional Mechanotransduction through the YAP/TAZ/Hippo Pathway as a Feature of Chronic Disease.Cells · 2020Review
- Mechanisms of Spindle Positioning: Lessons from Worms and Mammalian Cells.Biomolecules · 2019Review
- Developmental basis for intestinal barrier against the toxicity of graphene oxide.Particle and fibre toxicology · 2018Article
- A CRISPR Tagging-Based Screen Reveals Localized Players in Wnt-Directed Asymmetric Cell Division.Genetics · 2018Article
- Tumor suppressor APC is an attenuator of spindle-pulling forces duringProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Kif2 localizes to a subdomain of cortical endoplasmic reticulum that drives asymmetric spindle position.Nature communications · 2017Article
- Two populations of cytoplasmic dynein contribute to spindle positioning inThe Journal of cell biology · 2017Article
- Physical determinants of asymmetric cell divisions in the early development of Caenorhabditis elegans.Scientific reports · 2017Article
- Crosstalk of cell polarity signaling pathways.Protoplasma · 2017Review
- Multisite Phosphorylation of NuMA-Related LIN-5 Controls Mitotic Spindle Positioning in C. elegans.PLoS genetics · 2016Article
- Aurora A kinase regulates proper spindle positioning in C. elegans and in human cells.Journal of cell science · 2016Article
- The 14-3-3 protein PAR-5 regulates the asymmetric localization of the LET-99 spindle positioning protein.Developmental biology · 2016Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The position of the mitotic spindle controls the plane of cell cleavage and determines whether polarized cells divide symmetrically or asymmetrically. In animals, an evolutionarily conserved pathway of LIN-5 (homologues: Mud and NuMA), GPR-1/2 (homologues: Pins, LGN, AGS-3) and Gα mediates spindle positioning, and acts downstream of the conserved PAR-3-PAR-6-aPKC polarity complex. However, molecular interactions between polarity proteins and LIN-5-GPR-Gα remain to be identified. Here we describe a quantitative mass spectrometry approach for in vivo identification of protein kinase substrates. Applying this strategy to Caenorhabditis elegans embryos, we found that depletion of the polarity kinase PKC-3 results in markedly decreased levels of phosphorylation of a cluster of four LIN-5 serine residues. These residues are directly phosphorylated by PKC-3 in vitro. Phospho-LIN-5 co-localizes with PKC-3 at the anterior cell cortex and temporally coincides with a switch from anterior- to posterior-directed spindle movements in the one-cell embryo. LIN-5 mutations that prevent phosphorylation increase the extent of anterior-directed spindle movements, whereas phosphomimetic mutations decrease spindle migration. Our results indicate that anterior-located PKC-3 inhibits cortical microtubule pulling forces through direct phosphorylation of LIN-5. This molecular interaction between polarity and spindle-positioning proteins may be used broadly in cell cleavage plane determination.
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