C-terminal residues of skeletal muscle calsequestrin are essential for calcium binding and for skeletal ryanodine receptor inhibition

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    Abstract

    BACKGROUND: Skeletal muscle function depends on calcium signaling proteins in the sarcoplasmic reticulum (SR), including the calcium-binding protein calsequestrin (CSQ), the ryanodine receptor (RyR) calcium release channel, and skeletal triadin 95 kDa (trisk95) and junctin, proteins that bind to calsequestrin type 1 (CSQ1) and ryanodine receptor type 1 (RyR1). CSQ1 inhibits RyR1 and communicates store calcium load to RyR1 channels via trisk95 and/or junctin.

    METHODS: In this manuscript, we test predictions that CSQ1's acidic C-terminus contains binding sites for trisk95 and junctin, the major calcium binding domain, and that it determines CSQ1's ability to regulate RyR1 activity.

    RESULTS: Progressive alanine substitution of C-terminal acidic residues of CSQ1 caused a parallel reduction in the calcium binding capacity but did not significantly alter CSQ1's association with trisk95/junctin or influence its inhibition of RyR1 activity. Deletion of the final seven residues in the C-terminus significantly hampered calcium binding, significantly reduced CSQ's association with trisk95/junctin and decreased its inhibition of RyR1. Deletion of the full C-terminus further reduced calcium binding to CSQ1 altered its association with trisk95 and junctin and abolished its inhibition of RyR1.

    CONCLUSIONS: The correlation between the number of residues mutated/deleted and binding of calcium, trisk95, and junctin suggests that binding of each depends on diffuse ionic interactions with several C-terminal residues and that these interactions may be required for CSQ1 to maintain normal muscle function.

    Original languageEnglish
    Article number6
    Pages (from-to)1-12
    Number of pages12
    JournalSkeletal Muscle
    Volume5
    Issue number1
    DOIs
    Publication statusPublished - 2015

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    Calsequestrin
    Ryanodine Receptor Calcium Release Channel
    Skeletal Muscle
    Calcium
    Calcium-Binding Proteins
    Calcium Signaling
    Sarcoplasmic Reticulum
    Alanine
    Proteins
    Binding Sites
    Muscles

    Cite this

    @article{c4e6159a9e9a4fdc9cc548528ad20024,
    title = "C-terminal residues of skeletal muscle calsequestrin are essential for calcium binding and for skeletal ryanodine receptor inhibition",
    abstract = "BACKGROUND: Skeletal muscle function depends on calcium signaling proteins in the sarcoplasmic reticulum (SR), including the calcium-binding protein calsequestrin (CSQ), the ryanodine receptor (RyR) calcium release channel, and skeletal triadin 95 kDa (trisk95) and junctin, proteins that bind to calsequestrin type 1 (CSQ1) and ryanodine receptor type 1 (RyR1). CSQ1 inhibits RyR1 and communicates store calcium load to RyR1 channels via trisk95 and/or junctin.METHODS: In this manuscript, we test predictions that CSQ1's acidic C-terminus contains binding sites for trisk95 and junctin, the major calcium binding domain, and that it determines CSQ1's ability to regulate RyR1 activity.RESULTS: Progressive alanine substitution of C-terminal acidic residues of CSQ1 caused a parallel reduction in the calcium binding capacity but did not significantly alter CSQ1's association with trisk95/junctin or influence its inhibition of RyR1 activity. Deletion of the final seven residues in the C-terminus significantly hampered calcium binding, significantly reduced CSQ's association with trisk95/junctin and decreased its inhibition of RyR1. Deletion of the full C-terminus further reduced calcium binding to CSQ1 altered its association with trisk95 and junctin and abolished its inhibition of RyR1.CONCLUSIONS: The correlation between the number of residues mutated/deleted and binding of calcium, trisk95, and junctin suggests that binding of each depends on diffuse ionic interactions with several C-terminal residues and that these interactions may be required for CSQ1 to maintain normal muscle function.",
    keywords = "Ca binding protein, Calsequestrin, Ryanodine receptor, Sarcoplasmic reticulum, Skeletal muscle, Ca2+ binding protein",
    author = "Nicole BEARD",
    year = "2015",
    doi = "10.1186/s13395-015-0029-7",
    language = "English",
    volume = "5",
    pages = "1--12",
    journal = "Skeletal Muscle",
    issn = "2044-5040",
    publisher = "BioMed Central",
    number = "1",

    }

    TY - JOUR

    T1 - C-terminal residues of skeletal muscle calsequestrin are essential for calcium binding and for skeletal ryanodine receptor inhibition

    AU - BEARD, Nicole

    PY - 2015

    Y1 - 2015

    N2 - BACKGROUND: Skeletal muscle function depends on calcium signaling proteins in the sarcoplasmic reticulum (SR), including the calcium-binding protein calsequestrin (CSQ), the ryanodine receptor (RyR) calcium release channel, and skeletal triadin 95 kDa (trisk95) and junctin, proteins that bind to calsequestrin type 1 (CSQ1) and ryanodine receptor type 1 (RyR1). CSQ1 inhibits RyR1 and communicates store calcium load to RyR1 channels via trisk95 and/or junctin.METHODS: In this manuscript, we test predictions that CSQ1's acidic C-terminus contains binding sites for trisk95 and junctin, the major calcium binding domain, and that it determines CSQ1's ability to regulate RyR1 activity.RESULTS: Progressive alanine substitution of C-terminal acidic residues of CSQ1 caused a parallel reduction in the calcium binding capacity but did not significantly alter CSQ1's association with trisk95/junctin or influence its inhibition of RyR1 activity. Deletion of the final seven residues in the C-terminus significantly hampered calcium binding, significantly reduced CSQ's association with trisk95/junctin and decreased its inhibition of RyR1. Deletion of the full C-terminus further reduced calcium binding to CSQ1 altered its association with trisk95 and junctin and abolished its inhibition of RyR1.CONCLUSIONS: The correlation between the number of residues mutated/deleted and binding of calcium, trisk95, and junctin suggests that binding of each depends on diffuse ionic interactions with several C-terminal residues and that these interactions may be required for CSQ1 to maintain normal muscle function.

    AB - BACKGROUND: Skeletal muscle function depends on calcium signaling proteins in the sarcoplasmic reticulum (SR), including the calcium-binding protein calsequestrin (CSQ), the ryanodine receptor (RyR) calcium release channel, and skeletal triadin 95 kDa (trisk95) and junctin, proteins that bind to calsequestrin type 1 (CSQ1) and ryanodine receptor type 1 (RyR1). CSQ1 inhibits RyR1 and communicates store calcium load to RyR1 channels via trisk95 and/or junctin.METHODS: In this manuscript, we test predictions that CSQ1's acidic C-terminus contains binding sites for trisk95 and junctin, the major calcium binding domain, and that it determines CSQ1's ability to regulate RyR1 activity.RESULTS: Progressive alanine substitution of C-terminal acidic residues of CSQ1 caused a parallel reduction in the calcium binding capacity but did not significantly alter CSQ1's association with trisk95/junctin or influence its inhibition of RyR1 activity. Deletion of the final seven residues in the C-terminus significantly hampered calcium binding, significantly reduced CSQ's association with trisk95/junctin and decreased its inhibition of RyR1. Deletion of the full C-terminus further reduced calcium binding to CSQ1 altered its association with trisk95 and junctin and abolished its inhibition of RyR1.CONCLUSIONS: The correlation between the number of residues mutated/deleted and binding of calcium, trisk95, and junctin suggests that binding of each depends on diffuse ionic interactions with several C-terminal residues and that these interactions may be required for CSQ1 to maintain normal muscle function.

    KW - Ca binding protein

    KW - Calsequestrin

    KW - Ryanodine receptor

    KW - Sarcoplasmic reticulum

    KW - Skeletal muscle

    KW - Ca2+ binding protein

    UR - http://www.scopus.com/inward/record.url?scp=84926340609&partnerID=8YFLogxK

    UR - http://www.mendeley.com/research/cterminal-residues-skeletal-muscle-calsequestrin-essential-calcium-binding-skeletal-ryanodine-recept

    U2 - 10.1186/s13395-015-0029-7

    DO - 10.1186/s13395-015-0029-7

    M3 - Article

    VL - 5

    SP - 1

    EP - 12

    JO - Skeletal Muscle

    JF - Skeletal Muscle

    SN - 2044-5040

    IS - 1

    M1 - 6

    ER -