ArticleNature cell biology2015
PLK1-dependent activation of LRRK1 regulates spindle orientation by phosphorylating CDK5RAP2.
Article in Nature cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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48 citing papers in PubMed, 74 citations in OpenAlex.
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- Genome-wide association study and genomic selection for growth-related traits in Eastern oyster (Crassostrea virginica).BMC genomics · 2025Article
- In vitro reconstitution of a minimal human centrosome scaffold capable of forming and clustering microtubule asters.Journal of cell science · 2025Article
- Rapid effects of valproic acid on the fetal brain transcriptome: implications for brain development and autism.Translational psychiatry · 2024Article
- From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- Rapid effects of valproic acid on the fetal brain transcriptome: Implications for brain development and autism.Research square · 2024Article
- The mitotic spindle-related seven-gene predicts the prognosis and immune microenvironment of lung adenocarcinoma.Journal of cancer research and clinical oncology · 2023Article
- Structure and regulation of full-length human leucine-rich repeat kinase 1.Nature communications · 2023Article
- Autoinhibitory mechanism controls binding of centrosomin motif 1 to γ-tubulin ring complex.The Journal of cell biology · 2023Article
- Leucine Repeat Rich Kinase 1 Controls Osteoclast Activity by Managing Lysosomal Trafficking and Secretion.Biology · 2023Article
- Automated Immunofluorescence Staining for Analysis of Mitotic Stages and Division Orientation in Brain Sections.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Article
- An alternative splice isoform of mouse CDK5RAP2 induced cytoplasmic microtubule nucleation.IBRO neuroscience reports · 2022Article
- LRRK1-mediated NDEL1 phosphorylation promotes cilia disassembly via dynein-2-driven retrograde intraflagellar transport.Journal of cell science · 2022Article
- Genetic interaction between PLK1 and downstream MCPH proteins in the control of centrosome asymmetry and cell fate during neural progenitor division.Cell death and differentiation · 2022Article
- The ciliopathy protein CCDC66 controls mitotic progression and cytokinesis by promoting microtubule nucleation and organization.PLoS biology · 2022Article
- Pathogenic BRCA1 variants disrupt PLK1-regulation of mitotic spindle orientation.Nature communications · 2022Article
- Polo-like kinase 1 is related with malignant characteristics and inhibits macrophages infiltration in glioma.Frontiers in immunology · 2022Article
- γ-Tubulin in microtubule nucleation and beyond.Frontiers in cell and developmental biology · 2022Review
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7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Correct formation of the cell division axis requires the initial precise orientation of the mitotic spindle. Proper spindle orientation depends on centrosome maturation, and Polo-like kinase 1 (PLK1) is known to play a crucial role in this process. However, the molecular mechanisms that function downstream of PLK1 are not well understood. Here we show that LRRK1 is a PLK1 substrate that is phosphorylated on Ser 1790. PLK1 phosphorylation is required for CDK1-mediated activation of LRRK1 at the centrosomes, and this in turn regulates mitotic spindle orientation by nucleating the growth of astral microtubules from the centrosomes. Interestingly, LRRK1 in turn phosphorylates CDK5RAP2(Cep215), a human homologue of Drosophila Centrosomin (Cnn), in its γ-tubulin-binding motif, thus promoting the interaction of CDK5RAP2 with γ-tubulin. LRRK1 phosphorylation of CDK5RAP2 Ser 140 is necessary for CDK5RAP2-dependent microtubule nucleation. Thus, our findings provide evidence that LRRK1 regulates mitotic spindle orientation downstream of PLK1 through CDK5RAP2-dependent centrosome maturation.
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