title: A novel family of katanin-like 2 protein isoforms (KATNAL2), interacting with nucleotide-binding proteins Nubp1 and Nubp2, are key regulators of different MT-based processes in mammalian cells.
abstract: Katanins are microtubule (MT)-severing AAA proteins with high phylogenetic conservation throughout the eukaryotes. They have been functionally implicated in processes requiring MT remodeling, such as spindle assembly in mitosis and meiosis, assembly/disassembly of flagella and cilia and neuronal morphogenesis. Here, we uncover a novel family of katanin-like 2 proteins (KATNAL2) in mouse, consisting of five alternatively spliced isoforms encoded by the Katnal2 genomic locus. We further demonstrate that in vivo these isoforms are able to interact with themselves, with each other and moreover directly and independently with MRP/MinD-type P-loop NTPases Nubp1 and Nubp2, which are integral components of centrioles, negative regulators of ciliogenesis and implicated in centriole duplication in mammalian cells. We find KATNAL2 localized on interphase MTs, centrioles, mitotic spindle, midbody and the axoneme and basal body of sensory cilia in cultured murine cells. shRNAi of Katnal2 results in inefficient cytokinesis and severe phenotypes of enlarged cells and nuclei, increased numbers of centrioles and the manifestation of aberrant multipolar mitotic spindles, mitotic defects, chromosome bridges, multinuclearity, increased MT acetylation and an altered cell cycle pattern. Silencing or stable overexpression of KATNAL2 isoforms drastically reduces ciliogenesis. In conclusion, KATNAL2s are multitasking enzymes involved in the same cell type in critically important processes affecting cytokinesis, MT dynamics, and ciliogenesis and are also implicated in cell cycle progression.
authors.affiliation: Department of Biological Sciences, University of Cyprus, University Avenue 1, 1678, Nicosia, Cyprus.
authors.forename: Antonis
authors.initials: A
authors.lastname: Ververis
authors.affiliation: Department of Biological Sciences, University of Cyprus, University Avenue 1, 1678, Nicosia, Cyprus.
authors.forename: Andri
authors.initials: A
authors.lastname: Christodoulou
authors.affiliation: Department of Biological Sciences, University of Cyprus, University Avenue 1, 1678, Nicosia, Cyprus.
authors.forename: Maria
authors.initials: M
authors.lastname: Christoforou
authors.affiliation: Department of Biological Sciences, University of Cyprus, University Avenue 1, 1678, Nicosia, Cyprus.
authors.forename: Christina
authors.initials: C
authors.lastname: Kamilari
authors.affiliation: The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: Carsten W
authors.initials: CW
authors.lastname: Lederer
authors.affiliation: Department of Biological Sciences, University of Cyprus, University Avenue 1, 1678, Nicosia, Cyprus. santama@ucy.ac.cy.
authors.forename: Niovi
authors.initials: N
authors.lastname: Santama
mesh_terms: D000251:Adenosine Triphosphatases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002453:Cell Cycle; D018385:Centrosome / Q000378:metabolism / Q000648:ultrastructure; D002923:Cilia / Q000378:metabolism / Q000648:ultrastructure; D048749:Cytokinesis; D019204:GTP-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D020868:Gene Silencing; D007399:Interphase; D047908:Intracellular Signaling Peptides and Proteins; D000074201:Katanin; D051379:Mice; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D041681:NIH 3T3 Cells; D060066:Protein Interaction Maps; D020033:Protein Isoforms / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism / Q000648:ultrastructure; D015854:Up-Regulation
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C400289:NUBP2 protein, mouse; C400290:Nubp1 protein, mouse; D020033:Protein Isoforms; D000251:Adenosine Triphosphatases; D019204:GTP-Binding Proteins; C000607910:KATNAL2 protein, mouse; D000074201:Katanin
keywords: Cilia; Cytokinesis; Cytoskeleton; Katanin; Microtubule-severing enzymes