title: The non-catalytic domains of Drosophila katanin regulate its abundance and microtubule-disassembly activity.
abstract: Microtubule severing is a biochemical reaction that generates an internal break in a microtubule and regulation of microtubule severing is critical for cellular processes such as ciliogenesis, morphogenesis, and meiosis and mitosis. Katanin is a conserved heterodimeric ATPase that severs and disassembles microtubules, but the molecular determinants for regulation of microtubule severing by katanin remain poorly defined. Here we show that the non-catalytic domains of Drosophila katanin regulate its abundance and activity in living cells. Our data indicate that the microtubule-interacting and trafficking (MIT) domain and adjacent linker region of the Drosophila katanin catalytic subunit Kat60 cooperate to regulate microtubule severing in two distinct ways. First, the MIT domain and linker region of Kat60 decrease its abundance by enhancing its proteasome-dependent degradation. The Drosophila katanin regulatory subunit Kat80, which is required to stabilize Kat60 in cells, conversely reduces the proteasome-dependent degradation of Kat60. Second, the MIT domain and linker region of Kat60 augment its microtubule-disassembly activity by enhancing its association with microtubules. On the basis of our data, we propose that the non-catalytic domains of Drosophila katanin serve as the principal sites of integration of regulatory inputs, thereby controlling its ability to sever and disassemble microtubules.
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Kyle D
authors.initials: KD
authors.lastname: Grode
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Rogers
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D020134:Catalytic Domain; D002478:Cells, Cultured; D019327:Copper Sulfate / Q000494:pharmacology; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000074201:Katanin; D007976:Leupeptins / Q000494:pharmacology; D008870:Microtubules / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000378:metabolism; D020506:Untranslated Regions
chemical_list: D029721:Drosophila Proteins; D007976:Leupeptins; D012330:RNA, Double-Stranded; D020506:Untranslated Regions; D000251:Adenosine Triphosphatases; D000074201:Katanin; D019327:Copper Sulfate; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde