AI Article Synopsis
- NEK1 kinase plays a crucial role in ciliogenesis, mitosis, and DNA repair, with mutations linked to diseases like axial spondylometaphyseal dysplasia and amyotrophic lateral sclerosis.
- Research reveals that NEK1 and C21ORF2 form a strong complex in human cells, with specific regions in both proteins responsible for their interaction, which can be disrupted by pathogenic mutations.
- Mutations that impair NEK1's kinase activity or its partnership with C21ORF2 significantly impact ciliogenesis and homologous recombination, highlighting the importance of this complex in related diseases.
Article Abstract
The NEK1 kinase controls ciliogenesis, mitosis, and DNA repair, and mutations cause human diseases including axial spondylometaphyseal dysplasia and amyotrophic lateral sclerosis. mutations cause a similar pattern of human diseases, suggesting close functional links with Here, we report that endogenous NEK1 and C21ORF2 form a tight complex in human cells. A C21ORF2 interaction domain "CID" at the C-terminus of NEK1 is necessary for its association with C21ORF2 in cells, and pathogenic mutations in this region disrupt the complex. AlphaFold modelling predicts an extended binding interface between a leucine-rich repeat domain in C21ORF2 and the NEK1-CID, and our model may explain why pathogenic mutations perturb the complex. We show that NEK1 mutations that inhibit kinase activity or weaken its association with C21ORF2 severely compromise ciliogenesis, and that C21ORF2, like NEK1 is required for homologous recombination. These data enhance our understanding of how the NEK1 kinase is regulated, and they shed light on NEK1-C21ORF2-associated diseases.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10185812 | PMC |
| http://dx.doi.org/10.26508/lsa.202201740 | DOI Listing |
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Article Synopsis
- The study investigates the association between NEK1 gene polymorphisms and clinical features of sporadic Parkinson's disease (PD) in a northern Chinese population, using 510 PD patients and 510 healthy controls.
- Significant differences were found for the rs66509122 polymorphism, suggesting it may lower the risk for sporadic PD and is linked to depression and diabetes in specific patient subgroups.
- The rs4563461 polymorphism did not show a strong link to PD susceptibility but was associated with sleep disorders, indicating both SNPs may influence non-motor symptoms in PD.
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