Pin1 and PKMzeta sequentially control dendritic protein synthesis.
Pin1 and PKMzeta sequentially control dendritic protein synthesis.
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Pin1 和 PKMzeta 依次控制树突蛋白的合成。
DOI：
10.1126/scisignal.2000451
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发表时间：
2010
影响因子：
7.3
通讯作者：
Malter,JamesS
中科院分区：
文献类型：
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作者：
Westmark,PamelaR;Westmark,CaraJ;Wang,SuQing;Levenson,Jonathan;O'Riordan,KennethJ;Burger,Corinna;Malter,JamesS
某些形式的学习和记忆以及它们的电生理学相关，长时程增强（LTP），需要树突翻译。我们证明，Pin 1（蛋白质与NIMA 1相互作用），肽基脯氨酰异构酶，存在于树突棘和轴，并抑制蛋白质合成诱导的β-amatergic信号。Pin 1抑制增加树突状细胞的翻译，可能通过真核生物翻译起始因子4 E（eIF 4 E）和eIF 4 E结合蛋白1和2（4 E-BP 1/2）。与蛋白质合成增加一致，Pin−/−小鼠的海马切片具有正常的早期LTP（E-LTP），但与野生型对照相比，晚期LTP（L-LTP）显著增强。Pin 1 −/−小鼠大脑中的蛋白激酶C β（PKC β）和蛋白激酶M β（PKM β）增加，它们的活性是维持树突翻译所必需的。PKM β通过磷酸化丝氨酸16与Pin 1相互作用并抑制Pin 1。因此，谷氨酸诱导的树突状蛋白的合成依次受到Pin 1和PKM β信号的调节。
Some forms of learning and memory and their electrophysiologic correlate, long-term potentiation (LTP), require dendritic translation. We demonstrate that Pin1 (protein interacting with NIMA 1), a peptidyl-prolyl isomerase, is present in dendritic spines and shafts and inhibits protein synthesis induced by glutamatergic signaling. Pin1 suppression increased dendritic translation, possibly through eukaryotic translation initiation factor 4E (eIF4E) and eIF4E binding proteins 1 and 2 (4E-BP1/2). Consistent with increased protein synthesis, hippocampal slices from Pin−/−mice had normal early LTP (E-LTP) but significantly enhanced late LTP (L-LTP) compared to wild-type controls. Protein kinase C ζ (PKCζ) and protein kinase M ζ (PKMζ) were increased in Pin1−/−mouse brain, and their activity was required to maintain dendritic translation. PKMζ interacted with and inhibited Pin1 by phosphorylating serine 16. Therefore, glutamate-induced, dendritic protein synthesis is sequentially regulated by Pin1 and PKMζ signaling.