文章基本信息

标题：Identification of a family of calcium sensors as protein ligands of inositol trisphosphate receptor Ca2+ release channels
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作者：Jun Yang ; Sean McBride ; Don-On Daniel Mak 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：11
页码：7711-7716
DOI：10.1073/pnas.102006299
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The inositol trisphosphate (InsP3) receptor (InsP3R) is a ubiquitously expressed intracellular Ca2+ channel that mediates complex cytoplasmic Ca2+ signals, regulating diverse cellular processes, including synaptic plasticity. Activation of the InsP3R channel is normally thought to require binding of InsP3 derived from receptor-mediated activation of phosphatidylinositol lipid hydrolysis. Here we identify a family of neuronal Ca2+-binding proteins as high-affinity protein agonists of the InsP3R, which bind to the channel and activate gating in the absence of InsP3. CaBP/caldendrin, a subfamily of the EF-hand-containing neuronal calcium sensor family of calmodulin-related proteins, bind specifically to the InsP3-binding region of all three InsP3R channel isoforms with high affinity (Ka {approx} 25 nM) in a Ca2+-dependent manner (Ka {approx} 1 {micro}M). Binding activates single-channel gating as efficaciously as InsP3, dependent on functional EF-hands in CaBP. In contrast, calmodulin neither bound with high affinity nor activated channel gating. CaBP1 and the type 1 InsP3R associate in rat whole brain and cerebellum lysates, and colocalize extensively in subcellular regions in cerebellar Purkinje neurons. Thus, InsP3R-mediated Ca2+ signaling in cells is possible even in the absence of InsP3 generation, a process that may be particularly important in responding to and shaping changes in intracellular Ca2+ concentration by InsP3-independent pathways and for localizing InsP3-mediated Ca2+ signals to individual synapses.