80K-H Interacts with Inositol 1,4,5-Trisphosphate (IP3) Receptors and Regulates IP3-induced Calcium Release Activity

• Published in: The Journal of biological chemistry Vol. 284; no. 1; pp. 372 - 380
• Main Authors: Kawaai, Katsuhiro, Hisatsune, Chihiro, Kuroda, Yukiko, Mizutani, Akihiro, Tashiro, Tomoko, Mikoshiba, Katsuhiko
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.01.2009; American Society for Biochemistry and Molecular Biology
• Subjects: Adenosine Triphosphate - metabolism; Adenosylhomocysteinase - genetics; Adenosylhomocysteinase - metabolism; Animals; Calcium - metabolism; Calcium Channels - genetics; Calcium Channels - metabolism; Calcium Signaling - physiology; Calcium-Binding Proteins; Cerebellum - cytology; Cerebellum - metabolism; Chlorocebus aethiops; COS Cells; Cytochromes c - genetics; Cytochromes c - metabolism; Endoplasmic Reticulum - genetics; Endoplasmic Reticulum - metabolism; Glucosidases - genetics; Glucosidases - metabolism; Hippocampus - cytology; Hippocampus - metabolism; Humans; Huntingtin Protein; Inositol 1,4,5-Trisphosphate Receptors - genetics; Inositol 1,4,5-Trisphosphate Receptors - metabolism; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Lectins, C-Type - genetics; Lectins, C-Type - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Inbred ICR; Microsomes - metabolism; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurons - cytology; Neurons - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M805828200

Inositol 1,4,5-trisphosphate receptors (IP3Rs) are intracellular channel proteins that mediate calcium (Ca2+) release from the endoplasmic reticulum, and they are involved in many biological processes (e.g. fertilization, secretion, and synaptic plasticity). Recent reports show that IP3R activity is strictly regulated by several interacting molecules (e.g. IP3R binding protein released with inositol 1,4,5-trisphosphate, huntingtin, presenilin, DANGER, and cytochrome c), and perturbation of this regulation causes intracellular Ca2+ 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 IP3Rs by yeast two-hybrid screening. 80K-H directly interacted with IP3R type 1 (IP3R1) in vitro and co-immunoprecipitated with IP3R1 in cell lysates. Immunocytochemical and immunohistochemical staining revealed that 80K-H colocalized with IP3R1 in COS-7 cells and in hippocampal neurons. We also showed that the purified recombinant 80K-H protein directly enhanced IP3-induced Ca2+ release activity by a Ca2+ release assay using mouse cerebellar microsomes. Furthermore 80K-H was found to regulate ATP-induced Ca2+ release in living cells. Thus, our findings suggest that 80K-H is a novel regulator of IP3R activity, and it may contribute to neuronal functions.