title: 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.
abstract: The Katanin family of microtubule-severing enzymes is critical for remodeling microtubule-based structures that influence cell division, motility, morphogenesis and signaling. Katanin is composed of a catalytic p60 subunit (A subunit, KATNA1) and a regulatory p80 subunit (B subunit, KATNB1). The mammalian genome also encodes two additional A-like subunits (KATNAL1 and KATNAL2) and one additional B-like subunit (KATNBL1) that have remained poorly characterized. To better understand the factors and mechanisms controlling mammalian microtubule-severing, we have taken a mass proteomic approach to define the protein interaction module for each mammalian Katanin subunit and to generate the mammalian Katanin family interaction network (Katan-ome). Further, we have analyzed the function of the KATNBL1 subunit and determined that it associates with KATNA1 and KATNAL1, it localizes to the spindle poles only during mitosis and it regulates Katanin A subunit microtubule-severing activity in vitro Interestingly, during interphase, KATNBL1 is sequestered in the nucleus through an N-terminal nuclear localization signal. Finally KATNB1 was able to compete the interaction of KATNBL1 with KATNA1 and KATNAL1. These data indicate that KATNBL1 functions as a regulator of Katanin A subunit microtubule-severing activity during mitosis and that it likely coordinates with KATNB1 to perform this function.
authors.affiliation: From the ‡Department of Chemistry and Biochemistry, University of California, Los Angeles, California, 90095;
authors.forename: Keith
authors.initials: K
authors.lastname: Cheung
authors.affiliation: From the ‡Department of Chemistry and Biochemistry, University of California, Los Angeles, California, 90095;
authors.forename: Silvia
authors.initials: S
authors.lastname: Senese
authors.affiliation: From the ‡Department of Chemistry and Biochemistry, University of California, Los Angeles, California, 90095;
authors.forename: Jiaen
authors.initials: J
authors.lastname: Kuang
authors.affiliation: From the ‡Department of Chemistry and Biochemistry, University of California, Los Angeles, California, 90095;
authors.forename: Ngoc
authors.initials: N
authors.lastname: Bui
authors.affiliation: From the ‡Department of Chemistry and Biochemistry, University of California, Los Angeles, California, 90095;
authors.forename: Chayanid
authors.initials: C
authors.lastname: Ongpipattanakul
authors.affiliation: From the ‡Department of Chemistry and Biochemistry, University of California, Los Angeles, California, 90095;
authors.forename: Ankur
authors.initials: A
authors.lastname: Gholkar
authors.affiliation: §Pasarow Mass Spectrometry Laboratory, The Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, California 90095;
authors.forename: Whitaker
authors.initials: W
authors.lastname: Cohn
authors.affiliation: §Pasarow Mass Spectrometry Laboratory, The Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, California 90095;
authors.forename: Joseph
authors.initials: J
authors.lastname: Capri
authors.affiliation: §Pasarow Mass Spectrometry Laboratory, The Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, California 90095; ¶Molecular Biology Institute, University of California, Los Angeles, California, 90095; ‖Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California, 90095.
authors.forename: Julian P
authors.initials: JP
authors.lastname: Whitelegge
authors.affiliation: From the ‡Department of Chemistry and Biochemistry, University of California, Los Angeles, California, 90095; ¶Molecular Biology Institute, University of California, Los Angeles, California, 90095; ‖Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California, 90095 torres@chem.ucla.edu.
authors.forename: Jorge Z
authors.initials: JZ
authors.lastname: Torres
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D000074201:Katanin; D013058:Mass Spectrometry; D008540:Meiosis; D008870:Microtubules / Q000378:metabolism*; D060066:Protein Interaction Maps; D040901:Proteomics / Q000379:methods*
chemical_list: D000251:Adenosine Triphosphatases; C000620002:KATNB1 protein, human; C000620625:KATNBL1 protein, human; C570385:KATNA1 protein, human; C000600349:KATNAL1 protein, human; D000074201:Katanin