Neurabin is a synaptic protein linking p70 S6 kinase and the neuronal cytoskeleton
Neurabin is a synaptic protein linking p70 S6 kinase and the neuronal cytoskeleton
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DOI：
10.1073/pnas.95.14.8351
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发表时间：
1998-07-07
影响因子：
11.1
通讯作者：
Snyder, SH
中科院分区：
文献类型：
--
作者：
Burnett, PE;Blackshaw, S;Snyder, SH
P70 S6激酶(P70(S6K))是一种有丝分裂原激活的蛋白激酶，在mRNA翻译过程中起着核心作用。它生理性地磷酸化40S核糖体亚基的S6蛋白，响应有丝分裂刺激，是雷帕霉素敏感途径的下游成分，包括12-kDa FK506结合蛋白，包括雷帕霉素和12-kDa FK506结合蛋白靶标1，在这里，我们报告了神经组织特异性F-肌动蛋白结合蛋白(Neurabin)的鉴定，它是一种含有1,095个氨基酸的神经元浓缩蛋白，含有PDZ结构域并结合p70(S6K)。我们通过酵母双杂交分析和生化技术证明了Neurabin-p70(S6K)的相互作用，p70S6K和Neurabin共沉淀从转染的HEK293细胞中分离出来。Neurabin的定点突变涉及其PDZ结构域与p70S6K的相互作用，缺失p70的羧基末端5个氨基酸(S6K)可消除这种相互作用，共转染Neurabin可激活p70(S6K)激酶活性。原位杂交结果显示，Neurabin和p70S6K的mRNA在脑切片上有明显的共定位。大鼠脑亚细胞分离表明，Neurabin和p70(S6K)均定位于突触小体的可溶性部分。通过其PDZ结构域，神经元特异性神经肽可将p70(S6K)靶向神经末梢。
p70 S6 kinase (p70(S6k)) is a mitogen-activated protein kinase that plays a central role in the control of mRNA translation. It physiologically phosphorylates the S6 protein of the 40s ribosomal subunit in response to mitogenic stimuli and is a downstream component of the rapamycin-sensitive pathway, which includes the 12-kDa FK506 binding protein and includes rapamycin and the 12-kDa FK506 binding protein target 1, Here,,ve report the identification of neurabin (neural tissue-specific F-actin binding protein), a neuronally enriched protein of 1,095 amino acids that contains a PDZ domain and binds p70(S6k). We demonstrate the neurabin-p70(S6k) interaction by yeast two-hybrid analysis and biochemical techniques, p70S6k and neurabin coimmunoprecipitate from transfected HEK293 cells. Site-directed mutagenesis of neurabin implicates its PDZ domain in the interaction with p70S6k, and deletion of the carboxyl-terminal five amino acids of p70(S6k) abrogates the interaction, Cotransfection of neurabin in HEK293 cells activates p70(S6k) kinase activity. The mRNA of neurabin and p70S6k show striking colocalization in brain sections by in situ hybridization, Subcellular fractionation of rat brain demonstrates that neurabin and p70(S6k) both localize to the soluble fraction of synaptosomes. By way of its PDZ domain, the neuronal-specific neurabin may target p70(S6k) to nerve terminals.