1. Academic Validation
  2. 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

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

  • Mol Cell Proteomics. 2016 May;15(5):1658-69. doi: 10.1074/mcp.M115.056465.
Keith Cheung 1 Silvia Senese 1 Jiaen Kuang 1 Ngoc Bui 1 Chayanid Ongpipattanakul 1 Ankur Gholkar 1 Whitaker Cohn 2 Joseph Capri 2 Julian P Whitelegge 3 Jorge Z Torres 4
Affiliations

Affiliations

  • 1 From the ‡Department of Chemistry and Biochemistry, University of California, Los Angeles, California, 90095;
  • 2 §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;
  • 3 §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.
  • 4 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 [email protected].
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.

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