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Related Experiment Videos

Inositol trisphosphate receptor and Ca2+ signalling

K Mikoshiba1, T Furuichi, A Miyawaki

  • 1Department of Molecular Neurobiology, University of Tokyo, Japan.

Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
|June 29, 1993
PubMed
Summary

Inositol 1,4,5-trisphosphate receptor (InsP3-R) functions as a calcium (Ca2+) release channel. This study identifies InsP3-R as the P400 protein and details its structure, function, and regulation.

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Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Inositol 1,4,5-trisphosphate (InsP3) is a crucial second messenger mediating intracellular calcium (Ca2+) release.
  • The InsP3 receptor (InsP3-R) is the primary protein responsible for this calcium release.
  • Understanding InsP3-R's structure and function is vital for deciphering calcium signaling pathways.

Purpose of the Study:

  • To identify and characterize the InsP3 receptor (InsP3-R).
  • To elucidate the role of InsP3-R in calcium release from intracellular stores.
  • To investigate the structural and regulatory properties of InsP3-R.

Main Methods:

  • Purification and cDNA cloning of the InsP3 receptor.
  • Generation of a cell transfectant expressing InsP3-R.

Related Experiment Videos

  • Biochemical assays including lipid bilayer incorporation and immunogold labeling.
  • Cross-linking experiments and sequence conservation analysis.
  • Main Results:

    • InsP3-R is identical to the P400 protein, enriched in cerebellar Purkinje cells.
    • Expressed InsP3-R binds InsP3 with high affinity and mediates InsP3-induced Ca2+ release.
    • InsP3-R forms a homotetramer, localized to the endoplasmic reticulum.
    • Conserved N-terminal sequences are critical for InsP3 binding; novel subtypes exist.

    Conclusions:

    • InsP3-R functions as a ligand-gated Ca2+ release channel.
    • The P400 protein is the InsP3 receptor, a key component of calcium signaling.
    • Structural conservation and alternative splicing contribute to InsP3-R diversity and function.