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UNC-45A Breaks MT Lattice Independent of its Effect on Non-Muscle Myosin II

Habicht, Juri (författare)
Bradenburg Medical School - Theodor Fontane, Neuruppin, Germany;Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, MN 55455, USA
Mooneyham, Ashley (författare)
Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, MN 55455, USA
Hoshino, Asumi (författare)
Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, MN 55455, USA
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Shetty, Mihir (författare)
Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, MN 55455, USA
Zhang, Xiaonan (författare)
Bradenburg Medical School - Theodor Fontane, Neuruppin, Germany;Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, MN 55455, USA
Emmings, Edith (författare)
Bradenburg Medical School - Theodor Fontane, Neuruppin, Germany
Yang, Qing (författare)
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA
Coombes, Courtney (författare)
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA
Gardner, Melissa K. (författare)
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA
Bazzaro, Martina (författare)
Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, MN 55455, USA
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 (creator_code:org_t)
2020-01-01
2020
Engelska.
Ingår i: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137.
Relaterad länk:
https://doi.org/10.1...
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https://urn.kb.se/re...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • In invertebrates, UNC-45 regulates myosin stability and functions. Vertebrates have two distinct isoforms of the protein: UNC-45B, expressed in muscle cells only and UNC-45A, expressed in all cells and implicated in regulating both Non-Muscle Myosin II (NMII)- and microtubule (MT)-associated functions. Here we show that both, in vitro and in cells, UNC-45A binds to the MT lattice leading to MT bending, breakage and depolymerization. Furthermore, we show that UNC-45A destabilizes MTs independent of its NMII C-terminal binding domain and even in presence of the NMII inhibitor blebbistatin. These findings identified UNC-45A as a novel type of MT-severing protein with a not mutually exclusive but rather dual role in regulating NMII activity and MT stability. Because many human diseases, from cancer to neurodegenerative diseases, are caused by or associated with deregulation of MT stability our findings have profound implications in both, the biology of MTs as well as the biology of human diseases and possible therapeutic implications for their treatment.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

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