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Christina Anne Mitchell - One of the best experts on this subject based on the ideXlab platform.

  • four and a half LIM Protein 1 gene mutations cause four distinct human myopathies a comprehensive review of the clinical histological and pathological features
    Neuromuscular Disorders, 2011
    Co-Authors: Brendan Wilding, Colleen Elizabeth Darcy, Christina Anne Mitchell, Meagan Jane Mcgrath
    Abstract:

    Abstract Mutations in the four and a half LIM Protein 1 ( FHL 1) gene were recently identified as the cause of four distinct skeletal muscle diseases. Since the initial report outlining the first fhl1 mutation in 2008, over 25 different mutations have been identified in patients with reducing body myopathy, X-linked myopathy characterized by postural muscle atrophy, scapuloperoneal myopathy and Emery–Dreifuss muscular dystrophy. Reducing body myopathy was first described four decades ago, its underlying genetic cause was unknown until the discovery of fhl1 mutations. X-linked myopathy characterized by postural muscle atrophy is a novel disease where fhl1 mutations are the only cause. This review will profile each of the FHL1, with a comprehensive analysis of mutations, a comparison of the clinical and histopathological features and will present several hypotheses for the possible disease mechanism(s).

  • four and a half LIM Protein 1 binds myosin binding Protein c and regulates myosin filament formation and sarcomere assembly
    Journal of Biological Chemistry, 2006
    Co-Authors: Meagan Jane Mcgrath, Denny L Cottle, Belinda S Cowling, Imogen Denise Coghill, Maianh Nguyen, Jennifer M Dyson, Paul Anthony Robinson, Melissa Holdsworth, Edna C Hardeman, Christina Anne Mitchell
    Abstract:

    Four and a half LIM Protein 1 (FHL1/SLIM1) is highly expressed in skeletal and cardiac muscle; however, the function of FHL1 remains unknown. Yeast two-hybrid screening identified slow type skeletal myosin-binding Protein C as an FHL1 binding partner. Myosin-binding Protein C is the major myosin-associated Protein in striated muscle that enhances the lateral association and stabilization of myosin thick filaments and regulates actomyosin interactions. The interaction between FHL1 and myosin-binding Protein C was confirmed using co-immunoprecipitation of recombinant and endogenous Proteins. Recombinant FHL2 and FHL3 also bound myosin-binding Protein C. FHL1 impaired co-sedimentation of myosin-binding Protein C with reconstituted myosin filaments, suggesting FHL1 may compete with myosin for binding to myosin-binding Protein C. In intact skeletal muscle and isolated myofibrils, FHL1 localized to the I-band, M-line, and sarcolemma, co-localizing with myosin-binding Protein C at the sarcolemma in intact skeletal muscle. Furthermore, in isolated myofibrils FHL1 staining at the M-line appeared to extend partially into the C-zone of the A-band, where it co-localized with myosin-binding Protein C. Overexpression of FHL1 in differentiating C2C12 cells induced "sac-like" myotube formation (myosac), associated with impaired Z-line and myosin thick filament assembly. This phenotype was rescued by co-expression of myosin-binding Protein C. FHL1 knockdown using RNAi resulted in impaired myosin thick filament formation associated with reduced incorporation of myosin-binding Protein C into the sarcomere. This study identified FHL1 as a novel regulator of myosin-binding Protein C activity and indicates a role for FHL1 in sarcomere assembly.

  • skeletal muscle LIM Protein 1 sLIM1 fhl1 induces α5β1 integrin dependent myocyte elongation
    American Journal of Physiology-cell Physiology, 2003
    Co-Authors: Meagan Jane Mcgrath, Christina Anne Mitchell, Paul Anthony Robinson, Susan Brown
    Abstract:

    Skeletal muscle LIM Protein 1 (SLIM1/FHL1) contains four and a half LIM domains and is highly expressed in skeletal and cardiac muscle. Elevated SLIM1 mRNA expression has been associated with postn...

  • skeletal muscle LIM Protein 1 regulates integrin mediated myoblast adhesion spreading and migration
    American Journal of Physiology-cell Physiology, 2003
    Co-Authors: Paul Anthony Robinson, Meagan Jane Mcgrath, Susan Brown, Rajendra Gurung, Christina Anne Mitchell
    Abstract:

    The skeletal muscle LIM Protein 1 (SLIM1) is highly expressed in skeletal and cardiac muscle, and its expression is downregulated significantly in dilated human cardiomyopathy. However, the functio...

  • characterization of two isoforms of the skeletal muscle LIM Protein 1 sLIM1 localization of sLIM1 at focal adhesions and the isoform sLIMmer in the nucleus of myoblasts and cytoplasm of myotubes suggests distinct roles in the cytoskeleton and in nuclear cytoplasmic communication
    Journal of Biological Chemistry, 1999
    Co-Authors: Susan Brown, Meagan Jane Mcgrath, Rajendra Gurung, Lisa M Ooms, Margaret M Maimone, Christina Anne Mitchell
    Abstract:

    We have cloned and characterized a novel isoform of the skeletal muscle LIM Protein 1 (SLIM1), designated SLIMMER. SLIM1 contains an N-terminal single zinc finger followed by four LIM domains. SLIMMER is identical to SLIM1 over the first three LIM domains but contains a novel C-terminal 96 amino acids with three potential bipartite nuclear localization signals, a putative nuclear export sequence, and 27 amino acids identical to the RBP-J binding region of KyoT2, a murine isoform of SLIM1. SLIM1 localized to the cytosol of Sol8 myoblasts and myotubes. SLIMMER was detected in the nucleus of myoblasts and, following differentiation into myotubes, was exclusively cytosolic. Recombinant green fluorescent Protein-SLIM1 localized to the cytoplasm and associated with focal adhesions and actin filaments in COS-7 cells, while green fluorescent Protein-SLIMMER was predominantly nuclear. SLIMMER truncation mutants revealed that the first nuclear localization signal mediates nuclear localization. The addition of the proposed nuclear export sequence decreased the level of exclusively nuclear expression and increased cytosolic SLIMMER expression in COS-7 cells. The leucine-rich nuclear export signal was required for the export of SLIMMER from the nucleus of myoblasts to the cytoplasm of myotubes. Collectively, these results suggest distinct roles for SLIM1 and SLIMMER in focal adhesions and nuclear-cytoplasmic communication.

Meagan Jane Mcgrath - One of the best experts on this subject based on the ideXlab platform.

  • four and a half LIM Protein 1 gene mutations cause four distinct human myopathies a comprehensive review of the clinical histological and pathological features
    Neuromuscular Disorders, 2011
    Co-Authors: Brendan Wilding, Colleen Elizabeth Darcy, Christina Anne Mitchell, Meagan Jane Mcgrath
    Abstract:

    Abstract Mutations in the four and a half LIM Protein 1 ( FHL 1) gene were recently identified as the cause of four distinct skeletal muscle diseases. Since the initial report outlining the first fhl1 mutation in 2008, over 25 different mutations have been identified in patients with reducing body myopathy, X-linked myopathy characterized by postural muscle atrophy, scapuloperoneal myopathy and Emery–Dreifuss muscular dystrophy. Reducing body myopathy was first described four decades ago, its underlying genetic cause was unknown until the discovery of fhl1 mutations. X-linked myopathy characterized by postural muscle atrophy is a novel disease where fhl1 mutations are the only cause. This review will profile each of the FHL1, with a comprehensive analysis of mutations, a comparison of the clinical and histopathological features and will present several hypotheses for the possible disease mechanism(s).

  • four and a half LIM Protein 1 binds myosin binding Protein c and regulates myosin filament formation and sarcomere assembly
    Journal of Biological Chemistry, 2006
    Co-Authors: Meagan Jane Mcgrath, Denny L Cottle, Belinda S Cowling, Imogen Denise Coghill, Maianh Nguyen, Jennifer M Dyson, Paul Anthony Robinson, Melissa Holdsworth, Edna C Hardeman, Christina Anne Mitchell
    Abstract:

    Four and a half LIM Protein 1 (FHL1/SLIM1) is highly expressed in skeletal and cardiac muscle; however, the function of FHL1 remains unknown. Yeast two-hybrid screening identified slow type skeletal myosin-binding Protein C as an FHL1 binding partner. Myosin-binding Protein C is the major myosin-associated Protein in striated muscle that enhances the lateral association and stabilization of myosin thick filaments and regulates actomyosin interactions. The interaction between FHL1 and myosin-binding Protein C was confirmed using co-immunoprecipitation of recombinant and endogenous Proteins. Recombinant FHL2 and FHL3 also bound myosin-binding Protein C. FHL1 impaired co-sedimentation of myosin-binding Protein C with reconstituted myosin filaments, suggesting FHL1 may compete with myosin for binding to myosin-binding Protein C. In intact skeletal muscle and isolated myofibrils, FHL1 localized to the I-band, M-line, and sarcolemma, co-localizing with myosin-binding Protein C at the sarcolemma in intact skeletal muscle. Furthermore, in isolated myofibrils FHL1 staining at the M-line appeared to extend partially into the C-zone of the A-band, where it co-localized with myosin-binding Protein C. Overexpression of FHL1 in differentiating C2C12 cells induced "sac-like" myotube formation (myosac), associated with impaired Z-line and myosin thick filament assembly. This phenotype was rescued by co-expression of myosin-binding Protein C. FHL1 knockdown using RNAi resulted in impaired myosin thick filament formation associated with reduced incorporation of myosin-binding Protein C into the sarcomere. This study identified FHL1 as a novel regulator of myosin-binding Protein C activity and indicates a role for FHL1 in sarcomere assembly.

  • skeletal muscle LIM Protein 1 sLIM1 fhl1 induces α5β1 integrin dependent myocyte elongation
    American Journal of Physiology-cell Physiology, 2003
    Co-Authors: Meagan Jane Mcgrath, Christina Anne Mitchell, Paul Anthony Robinson, Susan Brown
    Abstract:

    Skeletal muscle LIM Protein 1 (SLIM1/FHL1) contains four and a half LIM domains and is highly expressed in skeletal and cardiac muscle. Elevated SLIM1 mRNA expression has been associated with postn...

  • skeletal muscle LIM Protein 1 regulates integrin mediated myoblast adhesion spreading and migration
    American Journal of Physiology-cell Physiology, 2003
    Co-Authors: Paul Anthony Robinson, Meagan Jane Mcgrath, Susan Brown, Rajendra Gurung, Christina Anne Mitchell
    Abstract:

    The skeletal muscle LIM Protein 1 (SLIM1) is highly expressed in skeletal and cardiac muscle, and its expression is downregulated significantly in dilated human cardiomyopathy. However, the functio...

  • characterization of two isoforms of the skeletal muscle LIM Protein 1 sLIM1 localization of sLIM1 at focal adhesions and the isoform sLIMmer in the nucleus of myoblasts and cytoplasm of myotubes suggests distinct roles in the cytoskeleton and in nuclear cytoplasmic communication
    Journal of Biological Chemistry, 1999
    Co-Authors: Susan Brown, Meagan Jane Mcgrath, Rajendra Gurung, Lisa M Ooms, Margaret M Maimone, Christina Anne Mitchell
    Abstract:

    We have cloned and characterized a novel isoform of the skeletal muscle LIM Protein 1 (SLIM1), designated SLIMMER. SLIM1 contains an N-terminal single zinc finger followed by four LIM domains. SLIMMER is identical to SLIM1 over the first three LIM domains but contains a novel C-terminal 96 amino acids with three potential bipartite nuclear localization signals, a putative nuclear export sequence, and 27 amino acids identical to the RBP-J binding region of KyoT2, a murine isoform of SLIM1. SLIM1 localized to the cytosol of Sol8 myoblasts and myotubes. SLIMMER was detected in the nucleus of myoblasts and, following differentiation into myotubes, was exclusively cytosolic. Recombinant green fluorescent Protein-SLIM1 localized to the cytoplasm and associated with focal adhesions and actin filaments in COS-7 cells, while green fluorescent Protein-SLIMMER was predominantly nuclear. SLIMMER truncation mutants revealed that the first nuclear localization signal mediates nuclear localization. The addition of the proposed nuclear export sequence decreased the level of exclusively nuclear expression and increased cytosolic SLIMMER expression in COS-7 cells. The leucine-rich nuclear export signal was required for the export of SLIMMER from the nucleus of myoblasts to the cytoplasm of myotubes. Collectively, these results suggest distinct roles for SLIM1 and SLIMMER in focal adhesions and nuclear-cytoplasmic communication.

Susan Brown - One of the best experts on this subject based on the ideXlab platform.

Paul Anthony Robinson - One of the best experts on this subject based on the ideXlab platform.

  • four and a half LIM Protein 1 binds myosin binding Protein c and regulates myosin filament formation and sarcomere assembly
    Journal of Biological Chemistry, 2006
    Co-Authors: Meagan Jane Mcgrath, Denny L Cottle, Belinda S Cowling, Imogen Denise Coghill, Maianh Nguyen, Jennifer M Dyson, Paul Anthony Robinson, Melissa Holdsworth, Edna C Hardeman, Christina Anne Mitchell
    Abstract:

    Four and a half LIM Protein 1 (FHL1/SLIM1) is highly expressed in skeletal and cardiac muscle; however, the function of FHL1 remains unknown. Yeast two-hybrid screening identified slow type skeletal myosin-binding Protein C as an FHL1 binding partner. Myosin-binding Protein C is the major myosin-associated Protein in striated muscle that enhances the lateral association and stabilization of myosin thick filaments and regulates actomyosin interactions. The interaction between FHL1 and myosin-binding Protein C was confirmed using co-immunoprecipitation of recombinant and endogenous Proteins. Recombinant FHL2 and FHL3 also bound myosin-binding Protein C. FHL1 impaired co-sedimentation of myosin-binding Protein C with reconstituted myosin filaments, suggesting FHL1 may compete with myosin for binding to myosin-binding Protein C. In intact skeletal muscle and isolated myofibrils, FHL1 localized to the I-band, M-line, and sarcolemma, co-localizing with myosin-binding Protein C at the sarcolemma in intact skeletal muscle. Furthermore, in isolated myofibrils FHL1 staining at the M-line appeared to extend partially into the C-zone of the A-band, where it co-localized with myosin-binding Protein C. Overexpression of FHL1 in differentiating C2C12 cells induced "sac-like" myotube formation (myosac), associated with impaired Z-line and myosin thick filament assembly. This phenotype was rescued by co-expression of myosin-binding Protein C. FHL1 knockdown using RNAi resulted in impaired myosin thick filament formation associated with reduced incorporation of myosin-binding Protein C into the sarcomere. This study identified FHL1 as a novel regulator of myosin-binding Protein C activity and indicates a role for FHL1 in sarcomere assembly.

  • skeletal muscle LIM Protein 1 sLIM1 fhl1 induces α5β1 integrin dependent myocyte elongation
    American Journal of Physiology-cell Physiology, 2003
    Co-Authors: Meagan Jane Mcgrath, Christina Anne Mitchell, Paul Anthony Robinson, Susan Brown
    Abstract:

    Skeletal muscle LIM Protein 1 (SLIM1/FHL1) contains four and a half LIM domains and is highly expressed in skeletal and cardiac muscle. Elevated SLIM1 mRNA expression has been associated with postn...

  • skeletal muscle LIM Protein 1 regulates integrin mediated myoblast adhesion spreading and migration
    American Journal of Physiology-cell Physiology, 2003
    Co-Authors: Paul Anthony Robinson, Meagan Jane Mcgrath, Susan Brown, Rajendra Gurung, Christina Anne Mitchell
    Abstract:

    The skeletal muscle LIM Protein 1 (SLIM1) is highly expressed in skeletal and cardiac muscle, and its expression is downregulated significantly in dilated human cardiomyopathy. However, the functio...

Tomi P. Mäkelä - One of the best experts on this subject based on the ideXlab platform.

  • clik1 a novel kinase targeted to actin stress fibers by the clp 36 pdz LIM Protein
    Journal of Cell Science, 2002
    Co-Authors: Tea Vallenius, Tomi P. Mäkelä
    Abstract:

    In this report we have characterized a novel, ubiquitously expressed kinase, Clik1, that is predominantly nuclear and undergoes autophosphorylation. Yeast two-hybrid analysis indicated a highly specific association between Clik1 and CLP-36, which was identified in 36 out of 37 Clik1-interacting clones. CLP-36 is a PDZ-LIM Protein that localizes to actin stress fibers in nonmuscle cells and associates with α-actinin via its PDZ-domain. The association of CLP-36 with Clik1, in turn, is mediated by the C-terminal part of CLP-36 containing the LIM domain, and association was not noted with the closely related ALP PDZ-LIM Protein. Interestingly, the association with CLP-36 led to relocalization of the otherwise nuclear Clik1 kinase to actin stress fibers, where it disrupted the periodic staining pattern of CLP-36. Taken together these results establish the CLP-36 PDZ-LIM Protein as an adapter, recruiting the Clik1 kinase to actin stress fibers in nonmuscle cells, and suggest that Clik1 represents a novel regulator of actin stress fibers.

  • CLP-36 PDZ-LIM Protein associates with nonmuscle alpha-actinin-1 and alpha-actinin-4.
    The Journal of biological chemistry, 2000
    Co-Authors: Tea Vallenius, Keijo Luukko, Tomi P. Mäkelä
    Abstract:

    Abstract The PDZ-LIM family of Proteins (Enigma/LMP-1, ENH, ZASP/Cypher, RIL, ALP, and CLP-36) has been suggested to act as adapters that direct LIM-binding Proteins to the cytoskeleton. Most interactions of PDZ-LIM Proteins with the cytoskeleton have been identified in striated muscle, where several PDZ-LIM Proteins are predominantly expressed. By contrast, CLP-36 mRNA is expressed in several nonmuscle tissues, and here we demonstrate high expression of CLP-36 in epithelial cells by in situ hybridization analysis. Our subcellular localization studies indicate that in nonmuscle cells, CLP-36 Protein localizes to actin stress fibers. This localization is mediated via the PDZ domain of CLP-36 that associates with the spectrin-like repeats of α-actinin. Interestingly, immunoprecipitation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis indicate that both nonmuscle α-actinin-1 and α-actinin-4 form complexes with CLP-36. The high expression of α-actinin-4 in the colon, together with these results, suggests a specific function for the α-actinin-4-CLP-36 complex in the colonic epithelium. More generally, results presented here demonstrate that the association of PDZ-LIM Proteins with the cytoskeleton extends to the actin stress fibers of nonmuscle cells.