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Hippocalcin acts as a possible suppressor of neuronal apoptosis via NAIP-caspase and MLK3-JNK cascades

Research Project

Project/Area Number 13680852
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionToho University

Principal Investigator

TAKAMATSU Ken  School of Medicine Professor, 医学部, 教授 (90154898)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥2,700,000 (Direct Cost: ¥2,700,000)
KeywordsHippocalcin / Apoptosis / Calcium / JNK / Two-hybrid / MLK3 / NAIP3 / 海馬 / 錐体細胞 / 細胞内シグナル
Research Abstract

Hippocalcin (HIP) is a member of neuronal calcium sensors family predominantly expressed in the hippocampal pyramidal cells. Primary cultured hippocampal neuron from HIP deficient (-/-) mice showed a low survivability compared to that from wild type (+/+) mice. Contrary, in the survivability of cultured glia, there is no difference between -/- and +/+ mice. Calcium influx into primary cultured neurons was induced by glutamate, high potassium and inomycin, and the influx and efflux processes were monitored using Fra2AM. Both processes were impaired in -/- mice. Contrary, both were accelerated in HIP over expressed COS7 cells. These indicate that HIP acts not only as a calcium buffer but also as calcium channel and pump activators. Glutamate- and high potassium- induced JNK activations in -/- hippocampal slices were much higher than those in +/+ slices, indicating that HIP acts as a possible calcium-dependent suppressor of JNK cascade. Then, we screened to search for HIP target proteins by using yeast two-hybrid system composed of mouse brain cDNA library. Among 3x10^6 transformants, 76 positive clones were obtained. Β-galactosidase expression analysis revealed that 12 clones interact with HIP. These clones were classified into mixed lineage kinase (MLK) 3 (7 clones), protein 1B; a transcription factor having f-box/WD40 domain (3 clones), NAIP (neuronal apoptosis inhibitory protein) 3 (3 clones) and complexin 2 by sequence analysis. MLK3 is a JNK activator, displayed the strongest interaction. HIP was found to interact with C-terminal Pro/Ser/Thr-rich region of MLK3. Whole HIP conformation involved in the interaction. Neural visinin-like protein (NVP) 1, 2 and 3, structurally related proteins to HIP, did not show the binding activity to MLK3, NAIP is known to be an inhibitor of caspase cascade that suppress the neuronal apoptosis. These indicate that HIP acts as a possible suppressor of neuronal apoptosis via NAIP-caspase and MLK3-JNK cascades.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] Hamashima, H. et al.: "Immunochemical assessment of neural visinin-like calcium-binding protein 3 expression in rat brain"Neurosci.Res.. 39. 133-143 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suda, S. et al.: "Potassium channel mRNAs with AU-rich elements and brain-specific expression"Biochem.Biophys.Res.Commun.. 291. 1265-1271 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tamura, T. et al.: "Circadian expression of hnRNP U, a nuclear multi-potent regulatory protein, in the murine suprachiasmatic nucleus"Neurosci.Lett.. 341. 111-114 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hamashima H. et al.: "Immunochemical assessment of neural visinin-like calcium-binding protein 3 expression in rat brain"Neurosci Res. 39. 133-143 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suda S. et al.: "Potassium channel mRNAs with AU-rich elements and brain-specific expression"Biochem Biophys Res Commun. 291. 1265-1271 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tamaru T. et al.: "Circadian expression of hnRNP U, a nuclear multi-potent regulatory protein, in the murine suprachiasmatic nucleus"Neurosci Lett. 341. 111-114 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tamaru, T., et al.: "Circadian expression of hnRNP U, a nuclear multi-potent regulatory protein, in the murine suprachiasmatic nucleus"Neurosci. Lett.. 341. 111-114 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hamashima, H.et al.: "Immunochemical assessment of neural visinin-like calcium-binding protein 3 expression in rat brain"Neurosci.Res.. 39. 133-143 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Suda, S.et al.: "Potassium channel mRNAs with AU-rich elements and brain-specific expression"Biochem.Biophys.Res.Commun.. 291. 1265-1271 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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