Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep39902
Title: Katanin p80, NuMA and cytoplasmic dynein cooperate to control microtubule dynamics
Authors: Jin, M
Pomp, O
Shinoda, T
Toba, S
Torisawa, T
Furuta, K
Oiwa, K
Yasunaga, T
Kitagawa, D
Matsumura, S
Miyata, T
Tan, T.T
Reversade, B 
Hirotsune, S
Keywords: adenosine triphosphatase
dynein adenosine triphosphatase
katanin p80, human
nuclear protein
Numa1 protein, mouse
small interfering RNA
animal
fibroblast
genetics
HeLa cell line
human
inbred mouse strain
induced pluripotent stem cell
metabolism
microtubule
mitosis
mouse
mutation
nerve cell
nervous system development
nervous system malformation
physiology
Adenosine Triphosphatases
Animals
Dyneins
Fibroblasts
HeLa Cells
Humans
Induced Pluripotent Stem Cells
Mice
Mice, Inbred Strains
Microtubules
Mitosis
Mutation
Nervous System Malformations
Neurogenesis
Neurons
Nuclear Proteins
RNA, Small Interfering
Issue Date: 2017
Publisher: Nature Publishing Group
Citation: Jin, M, Pomp, O, Shinoda, T, Toba, S, Torisawa, T, Furuta, K, Oiwa, K, Yasunaga, T, Kitagawa, D, Matsumura, S, Miyata, T, Tan, T.T, Reversade, B, Hirotsune, S (2017). Katanin p80, NuMA and cytoplasmic dynein cooperate to control microtubule dynamics. Scientific Reports 7 : 39902. ScholarBank@NUS Repository. https://doi.org/10.1038/srep39902
Rights: Attribution 4.0 International
Abstract: Human mutations in KATNB1 (p80) cause severe congenital cortical malformations, which encompass the clinical features of both microcephaly and lissencephaly. Although p80 plays critical roles during brain development, the underlying mechanisms remain predominately unknown. Here, we demonstrate that p80 regulates microtubule (MT) remodeling in combination with NuMA (nuclear mitotic apparatus protein) and cytoplasmic dynein. We show that p80 shuttles between the nucleus and spindle pole in synchrony with the cell cycle. Interestingly, this striking feature is shared with NuMA. Importantly, p80 is essential for aster formation and maintenance in vitro. siRNA-mediated depletion of p80 and/or NuMA induced abnormal mitotic phenotypes in cultured mouse embryonic fibroblasts and aberrant neurogenesis and neuronal migration in the mouse embryonic brain. Importantly, these results were confirmed in p80-mutant harboring patient-derived induced pluripotent stem cells and brain organoids. Taken together, our findings provide valuable insights into the pathogenesis of severe microlissencephaly, in which p80 and NuMA delineate a common pathway for neurogenesis and neuronal migration via MT organization at the centrosome/spindle pole. © The Author(s) 2017.
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/179743
ISSN: 2045-2322
DOI: 10.1038/srep39902
Rights: Attribution 4.0 International
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