RRC ID 19645
Author Kawaai K, Hisatsune C, Kuroda Y, Mizutani A, Tashiro T, Mikoshiba K.
Title 80K-H interacts with inositol 1,4,5-trisphosphate (IP3) receptors and regulates IP3-induced calcium release activity.
Journal J Biol Chem
Abstract 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.
Volume 284(1)
Pages 372-380
Published 2009-1-2
DOI 10.1074/jbc.M805828200
PII S0021-9258(20)68326-0
PMID 18990696
MeSH Adenosine Triphosphate / metabolism Adenosylhomocysteinase / genetics Adenosylhomocysteinase / metabolism Animals COS Cells Calcium / metabolism* Calcium Channels / genetics Calcium Channels / metabolism* Calcium Signaling / physiology* Calcium-Binding Proteins Cerebellum / cytology Cerebellum / metabolism Chlorocebus aethiops 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*
IF 4.238
Times Cited 32
Human and Animal Cells COS-7(RCB0539)