Recruitment of katanin p60 by phosphorylated NDEL1, an LIS1 interacting protein, is essential for mitotic cell division and neuronal migration

Toyo-oka, Kazuhito; Sasaki, Shinji; Yano, Yoshihisa; Mori, Daisuke; Kobayashi, Takuya; Toyoshima, Yoko Y.; Tokuoka, Suzumi M.; Ishii, Satoshi; Shimizu, Takao; Muramatsu, Masami; Hiraiwa, Noriko; Yoshiki, Atsushi; Wynshaw‐Boris, Anthony; Hirotsune, Shinji

doi:10.1093/hmg/ddi339

Cited by 93 publications

(109 citation statements)

References 57 publications

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“…Although it is purely speculative, it is also possible that p60/katanin and Aurora B may have a more intimate involvement in addition to being targeted for ubiquitination by the same E3 ligase. Aurora A kinase, an Aurora B-related kinase, was shown to phosphorylate NDEL1 at mitotic entry, after which NDEL1 is rapidly degraded by ubiquitin-dependent proteolysis (62,64). NDEL1 modulates recruitment of p60/katanin to the centrosome and regulates cytoplasmic dynein function in neurons (62).…”

Section: Discussionmentioning

confidence: 99%

“…Aurora A kinase, an Aurora B-related kinase, was shown to phosphorylate NDEL1 at mitotic entry, after which NDEL1 is rapidly degraded by ubiquitin-dependent proteolysis (62,64). NDEL1 modulates recruitment of p60/katanin to the centrosome and regulates cytoplasmic dynein function in neurons (62). Treatment of HeLa cells with an Aurora B kinase inhibitor, ZM447493, resulted in an increase in p60/katanin protein levels (supplemental Fig.…”

Section: Discussionmentioning

confidence: 99%

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The Cul3/Klhdc5 E3 Ligase Regulates p60/Katanin and Is Required for Normal Mitosis in Mammalian Cells

Cummings

Bentley

Perdue

et al. 2009

Journal of Biological Chemistry

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The proper regulation of factors involved in mitosis is crucial to ensure normal cell division. Levels and activities of proteins are regulated in many ways, one of which is ubiquitin-mediated protein degradation. E3 ubiquitin ligases are involved in targeting specific substrates for degradation by facilitating their ubiquitination. In seeking to elucidate additional biological roles for Cul3 we performed a two-hybrid screen and identified Ctb9/ KLHDC5 as a Cul3-interacting protein. Overexpression of Ctb9/KLHDC5 resulted in an increase in microtubule density as well as persistent microtubule bridges between post-mitotic cells. Conversely, down-regulation of Ctb9/KLHDC5 showed a pronounced reduction in microtubule density. Based on these observations, we examined the interactions between Cul3, Ctb9/KLHDC5, and the microtubule-severing protein, p60/katanin. Here we show that p60/katanin interacts with a complex consisting of Cul3 and Ctb9/KLHDC5, which results in ubiquitin laddering of p60/katanin. Also, Cul3-deficient cells or Ctb9/KLHDC5-deficient cells show an increase in p60/katanin levels, indicating that Cul3/Ctb9/KLHDC5 is required for efficient p60/katanin removal. We demonstrate a novel regulatory mechanism for p60/katanin that occurs at the level of targeted proteolysis to allow normal mitotic progression in mammalian cells.Due to the irreversible nature of protein degradation, ubiquitin-mediated proteolysis is an effective method to sequentially order cell cycle events. During ubiquitin-mediated protein degradation, the E1 5 ubiquitin-activating enzyme forms an ATP-dependent thioester bond with a ubiquitin molecule. The activated ubiquitin is subsequently transferred to an E2 ubiquitin-conjugating enzyme, which can either directly attach ubiquitin onto its substrate or act in concert with an E3 ubiquitin ligase to achieve the same end (1, 2). The E3 serves a dual function in recruiting the E2 ubiquitin-conjugating enzyme to the substrate and in positioning the two in close proximity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Cul3/Klhdc5 E3 Ligase Regulates p60/Katanin and Is Required for Normal Mitosis in Mammalian Cells

Cummings

Bentley

Perdue

et al. 2009

Journal of Biological Chemistry

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“…LIS1, NDEL1 and NDE1 localize to the centrosome [150][151][152][153] and in cells deficient for LIS1, dynein or NDEL1 the distance between the nucleus and centrosome is abnormally large. [158][159][160] This decoupling of the centrosome from the nucleus appears to be due to loss of a specific microtubule bundle known as the microtubule fork/ cage, which connects the two organelles together, 158,159 and is essential for nuclear migration. 161 Disruption of this structure and therefore nucleuscentrosome coupling may be one means by which LIS1/NDEL1 knockdown inhibits nuclear migration.…”

Section: Lis1 Ndel1 Nde1 and Disc1mentioning

confidence: 99%

“…LIS1 and NDEL1 also influence microtubule stability and organization 154,158,160,162,163 and are involved in microtubule-based transport in both anterograde and retrograde directions. 151,164 Knockdown of NDEL1 expression using RNA interference blocks neurite production, 75 which may result from defective tubulin cytoskeletal dynamics and/or deficient microtubule-based transport to the growing neurite tip.…”

Section: Lis1 Ndel1 Nde1 and Disc1mentioning

confidence: 99%

The DISC locus in psychiatric illness

et al. 2007

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The DISC locus is located at the breakpoint of a balanced t(1;11) chromosomal translocation in a large and unique Scottish family. This translocation segregates in a highly statistically significant manner with a broad diagnosis of psychiatric illness, including schizophrenia, bipolar disorder and major depression, as well as with a narrow diagnosis of schizophrenia alone. Two novel genes were identified at this locus and due to the high prevalence of schizophrenia in this family, they were named Disrupted-in-Schizophrenia-1 (DISC1) and Disrupted-in-Schizophrenia-2 (DISC2). DISC1 encodes a novel multifunctional scaffold protein, whereas DISC2 is a putative noncoding RNA gene antisense to DISC1. A number of independent genetic linkage and association studies in diverse populations support the original linkage findings in the Scottish family and genetic evidence now implicates the DISC locus in susceptibility to schizophrenia, schizoaffective disorder, bipolar disorder and major depression as well as various cognitive traits. Despite this, with the exception of the t(1;11) translocation, robust evidence for a functional variant(s) is still lacking and genetic heterogeneity is likely. Of the two genes identified at this locus, DISC1 has been prioritized as the most probable candidate susceptibility gene for psychiatric illness, as its protein sequence is directly disrupted by the translocation. Much research has been undertaken in recent years to elucidate the biological functions of the DISC1 protein and to further our understanding of how it contributes to the pathogenesis of schizophrenia. These data are the main subject of this review; however, the potential involvement of DISC2 in the pathogenesis of psychiatric illness is also discussed. A detailed picture of DISC1 function is now emerging, which encompasses roles in neurodevelopment, cytoskeletal function and cAMP signalling, and several DISC1 interactors have also been defined as independent genetic susceptibility factors for psychiatric illness. DISC1 is a hub protein in a multidimensional risk pathway for major mental illness, and studies of this pathway are opening up opportunities for a better understanding of causality and possible mechanisms of intervention. Molecular Psychiatry (2008) 13, 36-64; doi:10.1038/sj.mp.4002106; published online 2 October 2007 Keywords: schizophrenia; bipolar disorder; depression; DISC1; DISC2; mouse models Genetics of DISC1 discoverySt Clair et al. 1 first reported a Scottish family with a high loading of major mental illness, which cosegregates with a t(1;11) translocation. Long-term follow-up of this family over a period of 30 years has reported 87 family members, of whom 37 carry the translocation. 2 Of 29 individuals carrying the translocation, for whom psychiatric assessment was possible, 7 have a diagnosis of schizophrenia, 1 has a diagnosis of bipolar disorder and 10 cases of recurrent major depression were also reported. 2 Thus, 18 of 29 translocation carriers are diagnosed with major mental illness whereas none of...

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“…After transfection, granular neurons of either sex were subjected to incubation for 24 h in noncoated 24-well dish (Falcon; BD Biosciences Discovery Labware) before start of cell culture on the coated dish. Cerebellar granule cells of either sex were isolated as described previously (Hatten, 1985;Toyo-Oka et al, 2005) and were subjected to transfection at 10 5 based on standard protocols. Isolated granular neurons were treated with a CDK5 inhibitor, Roscivitine (Selleck; 20 M), or an Aurora-A inhibitor, Aurora-A Inhibitor I (Selleck; 0.17 M) or VX-680 (Selleck; 0.03 M).…”

Section: Methodsmentioning

confidence: 99%

Activation of Aurora-A Is Essential for Neuronal Migration via Modulation of Microtubule Organization

et al. 2012

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Neuronal migration is a critical feature to ensure proper location and wiring of neurons during cortical development. Postmitotic neurons migrate from the ventricular zone into the cortical plate to establish neuronal lamina in an “inside-out” gradient of maturation. Here, we report that the mitotic kinase Aurora-A is critical for the regulation of microtubule organization during neuronal migration via an Aurora-A–NDEL1 pathway in the mouse. Suppression of Aurora-A activity by inhibitors or siRNA resulted in severe impairment of neuronal migration of granular neurons. In addition,in uteroinjection of the Aurora-A kinase-dead mutant provoked defective migration of cortical neurons. Furthermore, we demonstrated that suppression of Aurora-A impaired microtubule modulation in migrating neurons. Interestingly, suppression of CDK5 by an inhibitor or siRNA reduced Aurora-A activity and NDEL1 phosphorylation by Aurora-A, which led to defective neuronal migration. We found that CDK5RAP2 is a key molecule that mediates functional interaction and is essential for centrosomal targeting of Aurora-A. Our observations demonstrated novel and surprising cross talk between Aurora-A and CDK5 during neuronal migration.

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Recruitment of katanin p60 by phosphorylated NDEL1, an LIS1 interacting protein, is essential for mitotic cell division and neuronal migration

Cited by 93 publications

References 57 publications

The Cul3/Klhdc5 E3 Ligase Regulates p60/Katanin and Is Required for Normal Mitosis in Mammalian Cells

The Cul3/Klhdc5 E3 Ligase Regulates p60/Katanin and Is Required for Normal Mitosis in Mammalian Cells

The DISC locus in psychiatric illness

Activation of Aurora-A Is Essential for Neuronal Migration via Modulation of Microtubule Organization

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