Novel interactions of CLN3 protein link Batten disease to dysregulation of fodrin-Na, K ATPase complex

Kristiina Uusi-Rauva, Kaisu Luiro, Kimmo Tanhuanpää, Outi Kopra, Pablo Martin-Vasallo, Aija Kyttälä, Anu Jalanko

    Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

    Kuvaus

    juvenile neuronal ceroid lipofuscinosis (JNCL, Batten disease) is the most common progressive neurodegenerative disorder of childhood. CLN3, the transmembrane protein underlying JNCL, is proposed to participate in multiple cellular events including membrane trafficking and cytoskeletal functions. We demonstrate here that CLN3 interacts with the plasma membrane-associated cytoskeletal and endocytic fodrin and the associated Na+, K+ ATPase. The ion pumping activity of Na+, K+ ATPase was unchanged in Cln3(-/-) mouse primary neurons. However, the immunostaining pattern of fodrin appeared abnormal in JNCL fibroblasts and Cln3(-/-) mouse brains suggesting disturbances in the fodrin cytoskeleton. Furthermore, the basal subcellular distribution as well as ouabain-induced endocytosis of neuron-specific Na+, K+ ATPase were remarkably affected in Cln3(-/-) mouse primary neurons. These data suggest that CLN3 is involved if the regulation of plasma membrane fodrin cytoskeleton and consequently, the plasma membrane association of Na+, K+ ATPase. Most of the processes regulated by multi functional fodrin and Na+, K+ ATPase are also affected in JNCL and Cln3-deficiency implicating that dysregulation of fodrin cytoskeleton and non-pumping functions of Na+, K+ ATPase may play a role in the neuronal degeneration in JNCL. (c) 2008 Published by Elsevier Inc.
    Alkuperäiskielienglanti
    LehtiExperimental Cell Research
    Vuosikerta314
    Numero15
    Sivut2895-2905
    Sivumäärä11
    ISSN0014-4827
    DOI - pysyväislinkit
    TilaJulkaistu - 2008
    OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

    Tieteenalat

    • 311 Peruslääketieteet
    • 312 Kliiniset lääketieteet
    • 318 Lääketieteen bioteknologia
    • 217 Lääketieteen tekniikka
    • 118 Biotieteet
    • 515 Psykologia

    Lainaa tätä

    Uusi-Rauva, Kristiina ; Luiro, Kaisu ; Tanhuanpää, Kimmo ; Kopra, Outi ; Martin-Vasallo, Pablo ; Kyttälä, Aija ; Jalanko, Anu. / Novel interactions of CLN3 protein link Batten disease to dysregulation of fodrin-Na, K ATPase complex. Julkaisussa: Experimental Cell Research. 2008 ; Vuosikerta 314, Nro 15. Sivut 2895-2905.
    @article{1cf62c1ed7874b0aa19ce137d7cb8ec7,
    title = "Novel interactions of CLN3 protein link Batten disease to dysregulation of fodrin-Na, K ATPase complex",
    abstract = "juvenile neuronal ceroid lipofuscinosis (JNCL, Batten disease) is the most common progressive neurodegenerative disorder of childhood. CLN3, the transmembrane protein underlying JNCL, is proposed to participate in multiple cellular events including membrane trafficking and cytoskeletal functions. We demonstrate here that CLN3 interacts with the plasma membrane-associated cytoskeletal and endocytic fodrin and the associated Na+, K+ ATPase. The ion pumping activity of Na+, K+ ATPase was unchanged in Cln3(-/-) mouse primary neurons. However, the immunostaining pattern of fodrin appeared abnormal in JNCL fibroblasts and Cln3(-/-) mouse brains suggesting disturbances in the fodrin cytoskeleton. Furthermore, the basal subcellular distribution as well as ouabain-induced endocytosis of neuron-specific Na+, K+ ATPase were remarkably affected in Cln3(-/-) mouse primary neurons. These data suggest that CLN3 is involved if the regulation of plasma membrane fodrin cytoskeleton and consequently, the plasma membrane association of Na+, K+ ATPase. Most of the processes regulated by multi functional fodrin and Na+, K+ ATPase are also affected in JNCL and Cln3-deficiency implicating that dysregulation of fodrin cytoskeleton and non-pumping functions of Na+, K+ ATPase may play a role in the neuronal degeneration in JNCL. (c) 2008 Published by Elsevier Inc.",
    keywords = "311 Basic medicine, 312 Clinical medicine, 318 Medical biotechnology, 217 Medical engineering, 118 Biological sciences, 515 Psychology",
    author = "Kristiina Uusi-Rauva and Kaisu Luiro and Kimmo Tanhuanp{\"a}{\"a} and Outi Kopra and Pablo Martin-Vasallo and Aija Kytt{\"a}l{\"a} and Anu Jalanko",
    year = "2008",
    doi = "10.1016/j.yexcr.2008.06.016",
    language = "English",
    volume = "314",
    pages = "2895--2905",
    journal = "Experimental Cell Research",
    issn = "0014-4827",
    publisher = "Elsevier Inc.",
    number = "15",

    }

    Novel interactions of CLN3 protein link Batten disease to dysregulation of fodrin-Na, K ATPase complex. / Uusi-Rauva, Kristiina; Luiro, Kaisu; Tanhuanpää, Kimmo; Kopra, Outi; Martin-Vasallo, Pablo; Kyttälä, Aija; Jalanko, Anu.

    julkaisussa: Experimental Cell Research, Vuosikerta 314, Nro 15, 2008, s. 2895-2905.

    Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

    TY - JOUR

    T1 - Novel interactions of CLN3 protein link Batten disease to dysregulation of fodrin-Na, K ATPase complex

    AU - Uusi-Rauva, Kristiina

    AU - Luiro, Kaisu

    AU - Tanhuanpää, Kimmo

    AU - Kopra, Outi

    AU - Martin-Vasallo, Pablo

    AU - Kyttälä, Aija

    AU - Jalanko, Anu

    PY - 2008

    Y1 - 2008

    N2 - juvenile neuronal ceroid lipofuscinosis (JNCL, Batten disease) is the most common progressive neurodegenerative disorder of childhood. CLN3, the transmembrane protein underlying JNCL, is proposed to participate in multiple cellular events including membrane trafficking and cytoskeletal functions. We demonstrate here that CLN3 interacts with the plasma membrane-associated cytoskeletal and endocytic fodrin and the associated Na+, K+ ATPase. The ion pumping activity of Na+, K+ ATPase was unchanged in Cln3(-/-) mouse primary neurons. However, the immunostaining pattern of fodrin appeared abnormal in JNCL fibroblasts and Cln3(-/-) mouse brains suggesting disturbances in the fodrin cytoskeleton. Furthermore, the basal subcellular distribution as well as ouabain-induced endocytosis of neuron-specific Na+, K+ ATPase were remarkably affected in Cln3(-/-) mouse primary neurons. These data suggest that CLN3 is involved if the regulation of plasma membrane fodrin cytoskeleton and consequently, the plasma membrane association of Na+, K+ ATPase. Most of the processes regulated by multi functional fodrin and Na+, K+ ATPase are also affected in JNCL and Cln3-deficiency implicating that dysregulation of fodrin cytoskeleton and non-pumping functions of Na+, K+ ATPase may play a role in the neuronal degeneration in JNCL. (c) 2008 Published by Elsevier Inc.

    AB - juvenile neuronal ceroid lipofuscinosis (JNCL, Batten disease) is the most common progressive neurodegenerative disorder of childhood. CLN3, the transmembrane protein underlying JNCL, is proposed to participate in multiple cellular events including membrane trafficking and cytoskeletal functions. We demonstrate here that CLN3 interacts with the plasma membrane-associated cytoskeletal and endocytic fodrin and the associated Na+, K+ ATPase. The ion pumping activity of Na+, K+ ATPase was unchanged in Cln3(-/-) mouse primary neurons. However, the immunostaining pattern of fodrin appeared abnormal in JNCL fibroblasts and Cln3(-/-) mouse brains suggesting disturbances in the fodrin cytoskeleton. Furthermore, the basal subcellular distribution as well as ouabain-induced endocytosis of neuron-specific Na+, K+ ATPase were remarkably affected in Cln3(-/-) mouse primary neurons. These data suggest that CLN3 is involved if the regulation of plasma membrane fodrin cytoskeleton and consequently, the plasma membrane association of Na+, K+ ATPase. Most of the processes regulated by multi functional fodrin and Na+, K+ ATPase are also affected in JNCL and Cln3-deficiency implicating that dysregulation of fodrin cytoskeleton and non-pumping functions of Na+, K+ ATPase may play a role in the neuronal degeneration in JNCL. (c) 2008 Published by Elsevier Inc.

    KW - 311 Basic medicine

    KW - 312 Clinical medicine

    KW - 318 Medical biotechnology

    KW - 217 Medical engineering

    KW - 118 Biological sciences

    KW - 515 Psychology

    U2 - 10.1016/j.yexcr.2008.06.016

    DO - 10.1016/j.yexcr.2008.06.016

    M3 - Article

    VL - 314

    SP - 2895

    EP - 2905

    JO - Experimental Cell Research

    JF - Experimental Cell Research

    SN - 0014-4827

    IS - 15

    ER -