期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 292, 期 42, 页码 17324-17336出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M117.788331
关键词
-
资金
- National Institutes of Health [CA68485, DK20593, DK58404, DK59637, EY08126]
Neuronal excitation can induce new mRNA transcription, a phenomenon called excitation-transcription (E-T) coupling. Among several pathways implicated in E-T coupling, activation of voltage-gated L-type Ca2+ channels (LTCCs) in the plasma membrane can initiate a signaling pathway that ultimately increases nuclear CREB phosphorylation and, in most cases, expression of immediate early genes. Initiation of this long-range pathway has been shown to require recruitment of Ca2+-sensitive enzymes to a nanodomain in the immediate vicinity of the LTCC by an unknown mechanism. Here, we show that activated Ca2+/calmodulin-dependent protein kinase II (CaMKII) strongly interacts with a novel binding motif in the N-terminal domain of Ca(V)1 LTCC alpha 1 subunitsthat is not conserved in Ca(V)2 or Ca(V)3 voltage-gated Ca2+ channel subunits. Mutations in the Ca(V)1.3 alpha 1 subunit N-terminal domain or in the CaMKII catalytic domain that largely prevent the in vitrointeraction also disrupt CaMKII association with intact LTCC complexes isolated by immunoprecipitation. Furthermore, these same mutations interfere with E-T coupling in cultured hippocampal neurons. Taken together, our findings define a novel molecular interaction with the neuronal LTCC that is required for the initiation of a long-range signal to the nucleus that is critical for learning and memory.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据