Neuronal apoptosis inhibitory protein: Structural requirements for hippocalcin binding and effects on survival of NGF-dependent sympathetic neurons

Dan Lindholm, E. A. Mercer, Liying Yu, Yuming Chen, Jyrki Kukkonen, Laura Korhonen, U. Arumae

    Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

    Sammanfattning

    Neuronal apoptosis inhibitory protein (NAIP) has been linked to the inherited disease, spinal muscular atrophy (SMA), which occurs in children with degeneration of the motorneurons. In the nervous system, NAIP is expressed by specific classes of neurons including spinal motorneurons. Recently, NAIP was shown to interact with hippocalcin, which belongs to the neuronal calcium sensor (NCS) protein family. Here we have studied this interaction in more detail, using deletions and a mutagenesis of the third baculovirus inhibitory repeat (BIR) motif in NAIP, and functional assays for neuronal death. The results showed that specific amino acids and the zinc finger domain in BIR3 are needed for efficient interaction of NAIP with hippocalcin. Cotransfections of NAIP-BIR3 and hippocalcin resulted in translocation and colocalisation of the two proteins in neuroblastoma cells. This was accompanied by an enhanced resistance towards cell death induced by high levels of calcium. In contrast, expression of NAIP-BIR3 and hippocalcin in sympathetic neurons did not protect against death induced by nerve growth factor (NGF) withdrawal. The results demonstrate a functional interaction of hippocalcin with NAIP-BIR3, which in neuroblastoma cells leads to rescue of cells after high intracellular calcium, but which in sympathetic neurons had no significant effect. The results indicate that NAIP in conjunction with hippocalcin can affect the survival of some, but not all neural cells, and this interaction may play a role in the neurodegenerative processes in SMA, and possible other human disorders.
    Originalspråkengelska
    TidskriftBiochimica et Biophysica Acta. Proteins and Proteomics
    Volym1600
    Utgåva1-2
    Sidor (från-till)138-47
    Antal sidor10
    ISSN1570-9639
    DOI
    StatusPublicerad - 2002
    MoE-publikationstypA1 Tidskriftsartikel-refererad

    Bibliografisk information

    Lindholm, Dan Mercer, Eric A Yu, Li Ying Chen, Yuming Kukkonen, Jyrki Korhonen, Laura Arumae, Urmas Research Support, Non-U.S. Gov't Netherlands Biochimica et biophysica acta Biochim Biophys Acta. 2002 Nov 4;1600(1-2):138-47.
    Volume:
    Proceeding volume:

    Vetenskapsgrenar

    • 118 Biovetenskaper

    Citera det här

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    title = "Neuronal apoptosis inhibitory protein: Structural requirements for hippocalcin binding and effects on survival of NGF-dependent sympathetic neurons",
    abstract = "Neuronal apoptosis inhibitory protein (NAIP) has been linked to the inherited disease, spinal muscular atrophy (SMA), which occurs in children with degeneration of the motorneurons. In the nervous system, NAIP is expressed by specific classes of neurons including spinal motorneurons. Recently, NAIP was shown to interact with hippocalcin, which belongs to the neuronal calcium sensor (NCS) protein family. Here we have studied this interaction in more detail, using deletions and a mutagenesis of the third baculovirus inhibitory repeat (BIR) motif in NAIP, and functional assays for neuronal death. The results showed that specific amino acids and the zinc finger domain in BIR3 are needed for efficient interaction of NAIP with hippocalcin. Cotransfections of NAIP-BIR3 and hippocalcin resulted in translocation and colocalisation of the two proteins in neuroblastoma cells. This was accompanied by an enhanced resistance towards cell death induced by high levels of calcium. In contrast, expression of NAIP-BIR3 and hippocalcin in sympathetic neurons did not protect against death induced by nerve growth factor (NGF) withdrawal. The results demonstrate a functional interaction of hippocalcin with NAIP-BIR3, which in neuroblastoma cells leads to rescue of cells after high intracellular calcium, but which in sympathetic neurons had no significant effect. The results indicate that NAIP in conjunction with hippocalcin can affect the survival of some, but not all neural cells, and this interaction may play a role in the neurodegenerative processes in SMA, and possible other human disorders.",
    keywords = "Animals Binding Sites Calcium-Binding Proteins/*metabolism Cell Survival Cells, Cultured Ganglia, Sympathetic/*cytology Hippocalcin Inhibitor of Apoptosis Proteins Mice Mutation Nerve Growth Factor/pharmacology Nerve Tissue Proteins/*chemistry/*metabolism/physiology Neuroblastoma Neuronal Apoptosis-Inhibitory Protein Neurons/cytology/drug effects Protein Binding Protein Structure, Tertiary Proteins/chemistry Repetitive Sequences, Amino Acid Sequence Deletion Tumor Cells, Cultured Two-Hybrid System Techniques, 118 Biological sciences",
    author = "Dan Lindholm and Mercer, {E. A.} and Liying Yu and Yuming Chen and Jyrki Kukkonen and Laura Korhonen and U. Arumae",
    note = "Lindholm, Dan Mercer, Eric A Yu, Li Ying Chen, Yuming Kukkonen, Jyrki Korhonen, Laura Arumae, Urmas Research Support, Non-U.S. Gov't Netherlands Biochimica et biophysica acta Biochim Biophys Acta. 2002 Nov 4;1600(1-2):138-47. Volume: Proceeding volume:",
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    Neuronal apoptosis inhibitory protein: Structural requirements for hippocalcin binding and effects on survival of NGF-dependent sympathetic neurons. / Lindholm, Dan; Mercer, E. A.; Yu, Liying; Chen, Yuming; Kukkonen, Jyrki; Korhonen, Laura; Arumae, U.

    I: Biochimica et Biophysica Acta. Proteins and Proteomics, Vol. 1600, Nr. 1-2, 2002, s. 138-47.

    Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

    TY - JOUR

    T1 - Neuronal apoptosis inhibitory protein: Structural requirements for hippocalcin binding and effects on survival of NGF-dependent sympathetic neurons

    AU - Lindholm, Dan

    AU - Mercer, E. A.

    AU - Yu, Liying

    AU - Chen, Yuming

    AU - Kukkonen, Jyrki

    AU - Korhonen, Laura

    AU - Arumae, U.

    N1 - Lindholm, Dan Mercer, Eric A Yu, Li Ying Chen, Yuming Kukkonen, Jyrki Korhonen, Laura Arumae, Urmas Research Support, Non-U.S. Gov't Netherlands Biochimica et biophysica acta Biochim Biophys Acta. 2002 Nov 4;1600(1-2):138-47. Volume: Proceeding volume:

    PY - 2002

    Y1 - 2002

    N2 - Neuronal apoptosis inhibitory protein (NAIP) has been linked to the inherited disease, spinal muscular atrophy (SMA), which occurs in children with degeneration of the motorneurons. In the nervous system, NAIP is expressed by specific classes of neurons including spinal motorneurons. Recently, NAIP was shown to interact with hippocalcin, which belongs to the neuronal calcium sensor (NCS) protein family. Here we have studied this interaction in more detail, using deletions and a mutagenesis of the third baculovirus inhibitory repeat (BIR) motif in NAIP, and functional assays for neuronal death. The results showed that specific amino acids and the zinc finger domain in BIR3 are needed for efficient interaction of NAIP with hippocalcin. Cotransfections of NAIP-BIR3 and hippocalcin resulted in translocation and colocalisation of the two proteins in neuroblastoma cells. This was accompanied by an enhanced resistance towards cell death induced by high levels of calcium. In contrast, expression of NAIP-BIR3 and hippocalcin in sympathetic neurons did not protect against death induced by nerve growth factor (NGF) withdrawal. The results demonstrate a functional interaction of hippocalcin with NAIP-BIR3, which in neuroblastoma cells leads to rescue of cells after high intracellular calcium, but which in sympathetic neurons had no significant effect. The results indicate that NAIP in conjunction with hippocalcin can affect the survival of some, but not all neural cells, and this interaction may play a role in the neurodegenerative processes in SMA, and possible other human disorders.

    AB - Neuronal apoptosis inhibitory protein (NAIP) has been linked to the inherited disease, spinal muscular atrophy (SMA), which occurs in children with degeneration of the motorneurons. In the nervous system, NAIP is expressed by specific classes of neurons including spinal motorneurons. Recently, NAIP was shown to interact with hippocalcin, which belongs to the neuronal calcium sensor (NCS) protein family. Here we have studied this interaction in more detail, using deletions and a mutagenesis of the third baculovirus inhibitory repeat (BIR) motif in NAIP, and functional assays for neuronal death. The results showed that specific amino acids and the zinc finger domain in BIR3 are needed for efficient interaction of NAIP with hippocalcin. Cotransfections of NAIP-BIR3 and hippocalcin resulted in translocation and colocalisation of the two proteins in neuroblastoma cells. This was accompanied by an enhanced resistance towards cell death induced by high levels of calcium. In contrast, expression of NAIP-BIR3 and hippocalcin in sympathetic neurons did not protect against death induced by nerve growth factor (NGF) withdrawal. The results demonstrate a functional interaction of hippocalcin with NAIP-BIR3, which in neuroblastoma cells leads to rescue of cells after high intracellular calcium, but which in sympathetic neurons had no significant effect. The results indicate that NAIP in conjunction with hippocalcin can affect the survival of some, but not all neural cells, and this interaction may play a role in the neurodegenerative processes in SMA, and possible other human disorders.

    KW - Animals Binding Sites Calcium-Binding Proteins/metabolism Cell Survival Cells, Cultured Ganglia, Sympathetic/cytology Hippocalcin Inhibitor of Apoptosis Proteins Mice Mutation Nerve Growth Factor/pharmacology Nerve Tissue Proteins/chemistry/metabolism/phy

    KW - 118 Biological sciences

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    DO - 10.1016/S1570-9639(02)00454-5

    M3 - Article

    VL - 1600

    SP - 138

    EP - 147

    JO - Biochimica et Biophysica Acta. Proteins and Proteomics

    JF - Biochimica et Biophysica Acta. Proteins and Proteomics

    SN - 1570-9639

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