The essential role of LIS1, NDEL1 and Aurora-A in polarity formation and microtubule organization during neurogensis

Department of Genetic Disease Research, Osaka City University Graduate School of Medicine, Abeno, Osaka, Japan.
Cell adhesion & migration (Impact Factor: 4.51). 04/2010; 4(2):180-4. DOI: 10.4161/cam.4.2.10715
Source: PubMed


Lissencephaly is a devastating neurological disorder caused by to defective neuronal migration. LIS1 (or PAFAH1B1), the gene mutated in lissencephaly patients and its binding protein NDEL1 were found to regulate cytoplasmic dynein function and localization. LIS1 and NDEL1 also play a pivotal role on a microtubule regulation and determination of cell polarity. For example, LIS1 is required for the precise control of mitotic spindle orientation in both neuroepithelial stem cells and radial glial progenitor cells. On the other hand, NDEL1 is essential for mitotic entry as an effector molecule of Aurora-A kinase. In addition, an atypical protein kinase C (aPKC)-Aurora-A-NDEL1 pathway is critical for the regulation of microtubule organization during neurite extension. These findings suggest that physiological functions of LIS1 and NDEL1 in neurons have been ascribed for proteins fundamentally required for cell cycle progression and control. In turn, cell cycle regulators may exert other functions during neurogenesis in a direct or an indirect fashion. Thus far, only a handful of cell cycle regulators have been shown to play physiological cell cycle-independent roles in neurons. Further identification of such proteins and elucidation of their underlying mechanisms of action will likely reveal novel concepts and/or patterns that provide a clear link between their seemingly distinct cell cycle and neuronal functions.

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Available from: Masami Yamada, Sep 10, 2015
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    • "Independently, other groups have found that atypical PKC activates AurA, allowing AurA to phosphorylate NDEL1 and promote microtubule remodeling during neurite extension (Mori et al., 2009). AurA has also been found to directly phos­ phorylate Par­6, which together with atypical PKC and Par­3 regulates asymmetric cell division and cell polarity (Ogawa et al., 2009; Yamada et al., 2010). These nonmitotic activities of AurA likely also contribute to deregulation of growth in tumor cells overexpressing AurA. "
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