Proteomic Analysis of the Mammalian Katanin Family of Microtubule-severing Enzymes Defines Katanin p80 subunit B-like 1 (KATNBL1) as a Regulator of Mammalian Katanin Microtubule-severing

Cheung, Keith; Senese, Silvia; Kuang, Jiaen; Bui, Ngoc B.; Ongpipattanakul, Chayanid; Gholkar, Ankur A.; Cohn, Whitaker; Capri, Joseph; Whitelegge, Julian P.; Torres, Jorge Z.

doi:10.1074/mcp.m115.056465

Cited by 46 publications

(79 citation statements)

References 63 publications

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“…The binding of cytoplasmic dynein by the N-terminal WD40 repeat domain of p80 has previously been reported by our group23. A previous proteomic analysis had suggested the interaction between NuMA and p8024; however, their direct binding evidence had not been reported. To confirm these findings, GFP or GFP-conjugated p80 fragments (Fig.…”

Section: Resultssupporting

confidence: 56%

Katanin p80, NuMA and cytoplasmic dynein cooperate to control microtubule dynamics

Jin

Pomp

Shinoda

et al. 2017

Sci Rep

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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.

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Section: Resultssupporting

confidence: 56%

Katanin p80, NuMA and cytoplasmic dynein cooperate to control microtubule dynamics

Jin

Pomp

Shinoda

et al. 2017

Sci Rep

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“…Within the cytosol, microtubules can only be cut by microtubule severing proteins such as katanins, spastins, and fidgetins (Roll-Mecak & McNally, 2010;Sharp & Ross, 2012;Zhang, Rogers, Buster, & Sharp, 2007). Katanins form a complex containing a regulatory subunit and a catalytic subunit (Cheung et al, 2016;Ghosh, Dasgupta, & Guha, 2012;Quarmby & Lohret, 1999). To sever microtubules, a regulatory subunit binds to the microtubule to recruit a katanin catalytic subunit that initiates microtubule severing (Cheung et al, 2016;Hartman et al, 1998;McNally, Bazirgan, & McNally, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Katanins form a complex containing a regulatory subunit and a catalytic subunit (Cheung et al, 2016;Ghosh, Dasgupta, & Guha, 2012;Quarmby & Lohret, 1999). To sever microtubules, a regulatory subunit binds to the microtubule to recruit a katanin catalytic subunit that initiates microtubule severing (Cheung et al, 2016;Hartman et al, 1998;McNally, Bazirgan, & McNally, 2000). We have shown that the regulatory subunit KATNB1 and one of the catalytic subunits KATNAL1 are involved in K. pneumoniae-triggered microtubule severing and that depletion of these proteins increased the number of host cells with intact microtubules.…”

Section: Discussionmentioning

confidence: 99%

Klebsiella pneumoniaedisassembles host microtubules in lung epithelial cells

Chua

Liou

Bogdan

et al. 2018

Cellular Microbiology

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Klebsiella pneumoniae raises significant concerns to the health care industry as these microbes are the source of widespread contamination of medical equipment, cause pneumonia as well as other multiorgan metastatic infections and have gained multidrug resistance. Despite soaring mortality rates, the host cell alterations occurring during these infections remain poorly understood. Here, we show that during in vitro and in vivo K. pneumoniae infections of lung epithelia, microtubules are severed and then eliminated. This destruction does not require direct association of K. pneumoniae with the host cells, as microtubules are disassembled in cells that are distant from the infecting bacteria. This microtubule dismantling is dependent on the K. pneumoniae (Kp) gene ytfL as non‐pathogenic Escherichia coli expressing Kp ytfL disassemble microtubules in the absence of K. pneumoniae itself. Our data points to the host katanin catalytic subunit A like 1 protein (KATNAL1) and the katanin regulatory subunit B1 protein (KATNB1) as the gatekeepers to the microtubule severing event as both proteins localise specifically to microtubule cut sites. Infected cells that had either of these proteins knocked out maintained intact microtubules. Taken together, we have identified a novel mechanism that a bacterial pathogen has exploited to cause microtubule destruction within the host epithelia.

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“…For instance, in sea urchins, whereas p60 alone exhibits MT-severing activity, MT severing is greatly stimulated by the Con80 domain . Likewise, KATNBL1 in humans, which contains only a Con80 domain, stimulates the MT-severing activity of the Katanin complex (Cheung et al, 2016). By contrast, the WD40 domain is dispensable for Katanin activity and rather plays a role in regulating the subcellular localization of p60 (Hartman and Vale, 1999).…”

Section: Discussionmentioning

confidence: 99%

Microtubule-severing activity of AAA+ ATPase Katanin is essential for female meiotic spindle assembly

Joly¹,

Martino²,

Gigant³

et al. 2016

Journal of Cell Science

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In most animals, female meiotic spindles are assembled in the absence of centrosomes. How microtubules (MTs) are organized into acentrosomal meiotic spindles is poorly understood. In Caenorhabditis elegans, assembly of female meiotic spindles requires MEI-1 and MEI-2, which constitute the microtubule-severing AAA+ ATPase Katanin. However, the role of MEI-2 is not known and whether MT severing is required for meiotic spindle assembly is unclear. Here, we show that the essential role of MEI-2 is to confer MT binding to Katanin, which in turn stimulates the ATPase activity of MEI-1, leading to MT severing. To test directly the contribution of MT severing to meiotic spindle assembly, we engineered Katanin variants that retained MT binding and MT bundling activities but that were inactive for MT severing. In vivo analysis of these variants showed disorganized microtubules that lacked focused spindle poles reminiscent of the Katanin loss-of-function phenotype, demonstrating that the MT-severing activity is essential for meiotic spindle assembly in C. elegans. Overall, our results reveal the essential role of MEI-2 and provide the first direct evidence supporting an essential role of MT severing in meiotic spindle assembly in C. elegans.

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Proteomic Analysis of the Mammalian Katanin Family of Microtubule-severing Enzymes Defines Katanin p80 subunit B-like 1 (KATNBL1) as a Regulator of Mammalian Katanin Microtubule-severing

Cited by 46 publications

References 63 publications

Katanin p80, NuMA and cytoplasmic dynein cooperate to control microtubule dynamics

Katanin p80, NuMA and cytoplasmic dynein cooperate to control microtubule dynamics

Klebsiella pneumoniaedisassembles host microtubules in lung epithelial cells

Microtubule-severing activity of AAA+ ATPase Katanin is essential for female meiotic spindle assembly

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