80K-H interacts with inositol 1,4,5-trisphosphate (IP 3) receptors and regulates IP 3-induced calcium release activity

Katsuhiro Kawaai, Chihiro Hisatsune, Yukiko Kuroda, Akihiro Mizutani, Tomoko Tashiro, Katsuhiko Mikoshiba

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36 Citations (Scopus)


Inositol 1,4,5-trisphosphate receptors (IP 3Rs) are intracellular channel proteins that mediate calcium (Ca 2+) release from the endoplasmic reticulum, and they are involved in many biological processes (e.g. fertilization, secretion, and synaptic plasticity). Recent reports show that IP 3R activity is strictly regulated by several interacting molecules (e.g. IP 3R binding protein released with inositol 1,4,5-trisphosphate, huntingtin, presenilin, DANGER, and cytochrome c), and perturbation of this regulation causes intracellular Ca 2+ elevation leading to several diseases (e.g. Huntington disease and Alzheimer disease). In this study, we identified protein kinase C substrate 80K-H (80K-H) to be a novel molecule interacting with the COOH-terminal tail of IP 3Rs by yeast two-hybrid screening. 80K-H directly interacted with IP 3R type 1 (IP 3R1) in vitro and co-immunoprecipitated with IP 3R1 in cell lysates. Immunocytochemical and immunohistochemical staining revealed that 80K-H colocalized with IP 3R1 in COS-7 cells and in hippocampal neurons. We also showed that the purified recombinant 80K-H protein directly enhanced IP 3-induced Ca 2+ release activity by a Ca 2+ release assay using mouse cerebellar microsomes. Furthermore 80K-H was found to regulate ATP-induced Ca 2+ release in living cells. Thus, our findings suggest that 80K-H is a novel regulator of IP 3R activity, and it may contribute to neuronal functions.

Original languageEnglish
Pages (from-to)372-380
Number of pages9
JournalJournal of Biological Chemistry
Issue number1
Publication statusPublished - 2009 Jan 2
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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