The specificity of the interaction between αB-crystallin and desmin filaments and its impact on filament aggregation and cell viability

Jayne L. Elliott, Ming Der Perng, Alan R. Prescott, Karen A. Jansen, Gijsje H. Koenderink, Roy A. Quinlan

    Research output: Contribution to journalArticle

    28 Citations (Scopus)

    Abstract

    CRYAB (aB-crystallin) is expressed in many tissues and yet the R120G mutation in CRYAB causes tissue-specific pathologies, namely cardiomyopathy and cataract. Here, we present evidence to demonstrate that there is a specific functional interaction of CRYAB with desmin intermediate filaments that predisposes myo-cytes to disease caused by the R120G mutation. We use a variety of biochemical and biophysical techniques to show that plant, animal and ascidian small heat-shock proteins (sHSPs) can interact with intermediate filaments. Nevertheless, the mutation R120G in CRYAB does specifically change that interaction when compared with equivalent substitutions in HSP27 (R140G) and into the Caenorhabditis elegans HSP16.2 (R95G). By transient transfection, we show that R120G CRYAB specifically promotes intermediate filament aggregation in MCF7 cells. The transient transfection of R120G CRYAB alone has no significant effect upon cell viability, although bundling of the endogenous intermediate filament network occurs and the mitochondria are concentrated into the perinuclear region. The combination of R120G CRYAB co-transfected with wild-type desmin, however, causes a significant reduction in cell viability. Therefore, we suggest that while there is an innate aBility of sHSPs to interact with and to bind to intermediate filaments, it is the specific combination of desmin and CRYAB that compromises cell viability and this is potentially the key to the muscle pathology caused by the R120G CRYAB.
    Original languageEnglish
    Article number20120375
    Number of pages15
    JournalPhilosophical Transactions of the Royal Society B - Biological Sciences
    Volume368
    Issue number1617
    DOIs
    Publication statusPublished - 2013

    Fingerprint

    crystallins
    intermediate filaments
    desmin
    Crystallins
    Desmin
    Intermediate Filaments
    Small Heat-Shock Proteins
    cell viability
    Cell Survival
    Agglomeration
    Cells
    Pathology
    Tissue
    transfection
    Mitochondria
    mutation
    heat shock proteins
    Mutation
    Transfection
    Muscle

    Keywords

    • Animals
    • Cell Line
    • Cell Survival
    • Cricetinae
    • Desmin
    • Glial Fibrillary Acidic Protein
    • Heat-Shock Proteins, Small
    • Humans
    • Hydrogen-Ion Concentration
    • Mice
    • Mutation
    • Protein Binding
    • Protein Conformation
    • Temperature
    • Vimentin
    • alpha-Crystallin B Chain

    Cite this

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    title = "The specificity of the interaction between αB-crystallin and desmin filaments and its impact on filament aggregation and cell viability",
    abstract = "CRYAB (aB-crystallin) is expressed in many tissues and yet the R120G mutation in CRYAB causes tissue-specific pathologies, namely cardiomyopathy and cataract. Here, we present evidence to demonstrate that there is a specific functional interaction of CRYAB with desmin intermediate filaments that predisposes myo-cytes to disease caused by the R120G mutation. We use a variety of biochemical and biophysical techniques to show that plant, animal and ascidian small heat-shock proteins (sHSPs) can interact with intermediate filaments. Nevertheless, the mutation R120G in CRYAB does specifically change that interaction when compared with equivalent substitutions in HSP27 (R140G) and into the Caenorhabditis elegans HSP16.2 (R95G). By transient transfection, we show that R120G CRYAB specifically promotes intermediate filament aggregation in MCF7 cells. The transient transfection of R120G CRYAB alone has no significant effect upon cell viability, although bundling of the endogenous intermediate filament network occurs and the mitochondria are concentrated into the perinuclear region. The combination of R120G CRYAB co-transfected with wild-type desmin, however, causes a significant reduction in cell viability. Therefore, we suggest that while there is an innate aBility of sHSPs to interact with and to bind to intermediate filaments, it is the specific combination of desmin and CRYAB that compromises cell viability and this is potentially the key to the muscle pathology caused by the R120G CRYAB.",
    keywords = "Animals, Cell Line, Cell Survival, Cricetinae, Desmin, Glial Fibrillary Acidic Protein, Heat-Shock Proteins, Small, Humans, Hydrogen-Ion Concentration, Mice, Mutation, Protein Binding, Protein Conformation, Temperature, Vimentin, alpha-Crystallin B Chain",
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    language = "English",
    volume = "368",
    journal = "Philosophical Transactions of the Royal Society B - Biological Sciences",
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    The specificity of the interaction between αB-crystallin and desmin filaments and its impact on filament aggregation and cell viability. / Elliott, Jayne L.; Perng, Ming Der; Prescott, Alan R.; Jansen, Karen A.; Koenderink, Gijsje H.; Quinlan, Roy A.

    In: Philosophical Transactions of the Royal Society B - Biological Sciences, Vol. 368, No. 1617, 20120375, 2013.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - The specificity of the interaction between αB-crystallin and desmin filaments and its impact on filament aggregation and cell viability

    AU - Elliott, Jayne L.

    AU - Perng, Ming Der

    AU - Prescott, Alan R.

    AU - Jansen, Karen A.

    AU - Koenderink, Gijsje H.

    AU - Quinlan, Roy A.

    N1 - Copyright 2013 Elsevier B.V., All rights reserved.

    PY - 2013

    Y1 - 2013

    N2 - CRYAB (aB-crystallin) is expressed in many tissues and yet the R120G mutation in CRYAB causes tissue-specific pathologies, namely cardiomyopathy and cataract. Here, we present evidence to demonstrate that there is a specific functional interaction of CRYAB with desmin intermediate filaments that predisposes myo-cytes to disease caused by the R120G mutation. We use a variety of biochemical and biophysical techniques to show that plant, animal and ascidian small heat-shock proteins (sHSPs) can interact with intermediate filaments. Nevertheless, the mutation R120G in CRYAB does specifically change that interaction when compared with equivalent substitutions in HSP27 (R140G) and into the Caenorhabditis elegans HSP16.2 (R95G). By transient transfection, we show that R120G CRYAB specifically promotes intermediate filament aggregation in MCF7 cells. The transient transfection of R120G CRYAB alone has no significant effect upon cell viability, although bundling of the endogenous intermediate filament network occurs and the mitochondria are concentrated into the perinuclear region. The combination of R120G CRYAB co-transfected with wild-type desmin, however, causes a significant reduction in cell viability. Therefore, we suggest that while there is an innate aBility of sHSPs to interact with and to bind to intermediate filaments, it is the specific combination of desmin and CRYAB that compromises cell viability and this is potentially the key to the muscle pathology caused by the R120G CRYAB.

    AB - CRYAB (aB-crystallin) is expressed in many tissues and yet the R120G mutation in CRYAB causes tissue-specific pathologies, namely cardiomyopathy and cataract. Here, we present evidence to demonstrate that there is a specific functional interaction of CRYAB with desmin intermediate filaments that predisposes myo-cytes to disease caused by the R120G mutation. We use a variety of biochemical and biophysical techniques to show that plant, animal and ascidian small heat-shock proteins (sHSPs) can interact with intermediate filaments. Nevertheless, the mutation R120G in CRYAB does specifically change that interaction when compared with equivalent substitutions in HSP27 (R140G) and into the Caenorhabditis elegans HSP16.2 (R95G). By transient transfection, we show that R120G CRYAB specifically promotes intermediate filament aggregation in MCF7 cells. The transient transfection of R120G CRYAB alone has no significant effect upon cell viability, although bundling of the endogenous intermediate filament network occurs and the mitochondria are concentrated into the perinuclear region. The combination of R120G CRYAB co-transfected with wild-type desmin, however, causes a significant reduction in cell viability. Therefore, we suggest that while there is an innate aBility of sHSPs to interact with and to bind to intermediate filaments, it is the specific combination of desmin and CRYAB that compromises cell viability and this is potentially the key to the muscle pathology caused by the R120G CRYAB.

    KW - Animals

    KW - Cell Line

    KW - Cell Survival

    KW - Cricetinae

    KW - Desmin

    KW - Glial Fibrillary Acidic Protein

    KW - Heat-Shock Proteins, Small

    KW - Humans

    KW - Hydrogen-Ion Concentration

    KW - Mice

    KW - Mutation

    KW - Protein Binding

    KW - Protein Conformation

    KW - Temperature

    KW - Vimentin

    KW - alpha-Crystallin B Chain

    UR - http://www.scopus.com/inward/record.url?scp=84875444277&partnerID=8YFLogxK

    U2 - 10.1098/rstb.2012.0375

    DO - 10.1098/rstb.2012.0375

    M3 - Article

    VL - 368

    JO - Philosophical Transactions of the Royal Society B - Biological Sciences

    JF - Philosophical Transactions of the Royal Society B - Biological Sciences

    SN - 0962-8436

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    M1 - 20120375

    ER -