Protein kinase Mζ synthesis from a brain mRNA encoding an independent protein kinase Cζ catalytic domain -: Implications for the molecular mechanism of memory
Protein kinase Mζ synthesis from a brain mRNA encoding an independent protein kinase Cζ catalytic domain -: Implications for the molecular mechanism of memory
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DOI：
10.1074/jbc.m307065200
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发表时间：
2003-10-10
影响因子：
4.8
通讯作者：
Sacktor, TC
中科院分区：
文献类型：
--
作者：
Hernandez, AI;Blace, N;Sacktor, TC
蛋白激酶Mzeta（PKMzeta）是新近发现的一种蛋白激酶C（PKC），在维持果蝇海马长时程增强（LTP）和记忆持续性中起重要作用。PKMzeta是非典型PKCzeta同种型的独立催化结构域，并且在突触处产生长期作用，因为它是持续活性的，缺乏来自PKCzeta的调节结构域的自身抑制。PKM被认为是PKC的蛋白水解片段。在这里，我们报告说，大脑PKMzeta是一个新的PKC亚型，合成的PKMzeta mRNA编码的PKCzeta催化结构域没有调节结构域。多种zeta特异性抗血清显示，PKMzeta在大鼠前脑中表达为zeta的主要形式，几乎不存在全长PKCzeta。PKCzeta基因敲除小鼠，其中调控结构域被破坏，催化结构域保留，仍然表达脑PKMzeta，表明这种形式的PKM不是PKCzeta蛋白水解片段。此外，大脑PKMzeta的分布与PKCzeta mRNA无关，而是与另一种被认为不能产生蛋白质的zeta RNA转录物相关。然而，这种RNA的体外翻译产生与大脑中相同分子量的PKMzeta。海马切片的代谢标记显示LTP中PKMzeta的从头合成增加。由于PKMzeta是一种以自主活性形式合成的激酶，并且对于维持LTP是必要的和足够的，因此它可以作为将基因表达直接耦合到突触可塑性的链接的例子。
Protein kinase Mzeta (PKMzeta) is a newly described form of PKC that is necessary and sufficient for the maintenance of hippocampal long term potentiation (LTP) and the persistence of memory in Drosophila. PKMzeta is the independent catalytic domain of the atypical PKCzeta isoform and produces long term effects at synapses because it is persistently active, lacking autoinhibition from the regulatory domain of PKCzeta. PKM has been thought of as a proteolytic fragment of PKC. Here we report that brain PKMzeta is a new PKC isoform, synthesized from a PKMzeta mRNA encoding a PKCzeta catalytic domain without a regulatory domain. Multiple zeta-specific antisera show that PKMzeta is expressed in rat forebrain as the major form of zeta in the near absence of full-length PKCzeta. A PKCzeta knockout mouse, in which the regulatory domain was disrupted and catalytic domain spared, still expresses brain PKMzeta, indicating that this form of PKM is not a PKCzeta proteolytic fragment. Furthermore, the distribution of brain PKMzeta does not correlate with PKCzeta mRNA but instead with an alternate zeta RNA transcript thought incapable of producing protein. In vitro translation of this RNA, however, generates PKMzeta of the same molecular weight as that in brain. Metabolic labeling of hippocampal slices shows increased de novo synthesis of PKMzeta in LTP. Because PKMzeta is a kinase synthesized in an autonomously active form and is necessary and sufficient for maintaining LTP, it serves as an example of a link coupling gene expression directly to synaptic plasticity.