LIS1 is mutated in the human neuronal migration defect lissencephaly and along with NDEL1 (formerly NUDEL) participates in the regulation of cytoplasmic dynein function during neuronal development. Targeted disruption of Ndel1 suggested that NDEL1 could have other molecular targets that regulate microtubule organization for proper neuronal migration. To further understanding the molecular mechanism of LIS1 and lissencephaly, we identified the katanin p60 microtubule-severing protein as an additional molecular target of NDEL1. We demonstrate that phosphorylation of NDEL1 by Cdk5 facilitates interaction between NDEL1 and p60, suggesting that P-NDEL1 regulates the distribution of katanin p60. Abnormal accumulation of p60 in nucleus of Ndel1 null mutants supports an essential role of NDEL1 in p60 regulation. Complete loss of NDEL1 or expression of dominant negative mutants of p60 in migrating neurons results in defective migration and elongation of nuclear-centrosomal distance. Our results suggest that NDEL1 is essential for mitotic cell division and neuronal migration not only via regulation of cytoplasmic dynein function but also by modulation of katanin p60 localization and function.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/hmg/ddi339 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Tubulin glutamylation regulates axon guidance via the selective tuning of microtubule-severing enzymes.
EMBO J
January 2025
Sorbonne Université, INSERM U1130, CNRS UMR8246, Neuroscience Paris Seine - Institut de Biologie Paris-Seine (NPS-IBPS), Paris, France.
The microtubule cytoskeleton is a major driving force of neuronal circuit development. Fine-tuned remodelling of this network by selective activation of microtubule-regulating proteins, including microtubule-severing enzymes, has emerged as a central process in neuronal wiring. Tubulin posttranslational modifications control both microtubule properties and the activities of their interacting proteins.
View Article and Find Full Text PDFExploring Novel Genomic Loci and Candidate Genes Associated with Plant Height in Bulgarian Bread Wheat via Multi-Model GWAS.
Plants (Basel)
October 2024
Institute of Plant Physiology and Genetics, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Block 21, 1113 Sofia, Bulgaria.
Article Synopsis
- Plant height (PH) is crucial for crop breeding, impacting both straw and grain yield in wheat, and this study aims to enhance understanding of the genetic factors influencing PH by using advanced GWAS techniques on diverse Bulgarian bread wheat varieties.
- The research identified 25 quantitative trait loci (QTL) related to PH across 14 chromosomes, highlighting 21 environmentally stable quantitative trait nucleotides (QTNs) and novel genomic regions with no previously known associations, which could be significant for future breeding efforts.
- Noteworthy findings include a haplotype block on chromosome 6A that contains both height-reducing and height-promoting QTN loci, indicating complex genetic interactions and potential pathways
Microtubule-binding domains in Katanin p80 subunit are essential for severing activity in C. elegans.
J Cell Biol
April 2024
Université Paris Cité, CNRS, Institut Jacques Monod , Paris, France.
Microtubule-severing enzymes (MSEs), such as Katanin, Spastin, and Fidgetin play essential roles in cell division and neurogenesis. They damage the microtubule (MT) lattice, which can either destroy or amplify the MT cytoskeleton, depending on the cellular context. However, little is known about how they interact with their substrates.
View Article and Find Full Text PDFCrystal structure of the Arabidopsis SPIRAL2 C-terminal domain reveals a p80-Katanin-like domain.
PLoS One
January 2024
Department of Biology, University of North Carolina, Chapel Hill, North Carolina, United States of America.
Epidermal cells of dark-grown plant seedlings reorient their cortical microtubule arrays in response to blue light from a net lateral orientation to a net longitudinal orientation with respect to the long axis of cells. The molecular mechanism underlying this microtubule array reorientation involves katanin, a microtubule severing enzyme, and a plant-specific microtubule associated protein called SPIRAL2. Katanin preferentially severs longitudinal microtubules, generating seeds that amplify the longitudinal array.
View Article and Find Full Text PDFA potential posttranscriptional regulator for p60-katanin: miR-124-3p.
Cytoskeleton (Hoboken)
December 2023
Department of Molecular Biology and Genetics, Faculty of Science, Mugla Sitki Kocman University, Mugla, Turkey.
Katanin is a microtubule severing protein belonging to the ATPase family and consists of two subunits; p60-katanin synthesized by the KATNA1 gene and p80-katanin synthesized by the KATNB1 gene. Microtubule severing is one of the mechanisms that allow the reorganization of microtubules depending on cellular needs. While this reorganization of microtubules is associated with mitosis in dividing cells, it primarily takes part in the formation of structures such as axons and dendrites in nondividing mature neurons.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!