Differential expression and regulation of myristoylated alanine-rich C kinase substrate (MARCKS) in the hippocampus of C57/BL6J and DBA/2J mice.
Differential expression and regulation of myristoylated alanine-rich C kinase substrate (MARCKS) in the hippocampus of C57/BL6J and DBA/2J mice.
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C57/BL6J 和 DBA/2J 小鼠海马中肉豆蔻酰化富含丙氨酸的 C 激酶底物 (MARCKS) 的差异表达和调节。
DOI：
10.1046/j.1471-4159.2003.01700.x
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发表时间：
2003
影响因子：
4.7
通讯作者：
Lenox,RobertH
中科院分区：
文献类型：
--
作者：
McNamara,RobertK;Vasquez,PatriciaA;Mathe,AleksanderA;Lenox,RobertH
豆蔻酰化富含丙氨酸的C激酶底物（MARCKS）是脑中主要的蛋白激酶C（PKC）底物，其结合质膜内表面、钙调蛋白并交联丝状肌动蛋白，所有这些均以PKC磷酸化可逆的方式进行。MARCKS与海马依赖性学习和长时程增强（LTP）有关。先前的研究表明，DBA/2小鼠表现出较差的空间/背景学习，海马LTP受损，海马苔藓纤维发育不全，以及海马PKC活性和表达相对于C57 BL/6小鼠降低。在本研究中，我们评估的表达（mRNA和蛋白质）和亚细胞分布（膜和cytolsol）MARCKS在海马和额叶皮质的C57 BL/6和DBA/2小鼠使用定量蛋白质印迹。在海马，总MARCKS mRNA和蛋白质水平在C57 BL/6 J小鼠显着较低（约45%）相比，DBA/2 J小鼠，和MARCKS蛋白主要是在胞浆级分中观察。MARCKS在额叶皮层的表达在不同品系之间没有显著差异。为了研究MARCKS亚细胞分布的动态调节，来自每个品系的小鼠经受60 min束缚应激，24 h后测定MARCKS亚细胞分布。 束缚应激导致C57 BL/6 J海马体中膜MARCKS表达显著降低，但DBA/2 J海马体中没有，尽管血清皮质酮的应激诱导增加相似。约束应力不影响细胞溶质或总MARCKS水平在任何一个菌株。同样，大鼠的束缚应激（30分钟）也诱导了海马但不是额叶皮质中膜MARCKS的显著减少，但不是总MARCKS或胞质MARCKS。 在大鼠中，应激暴露前的慢性锂处理降低了海马MARCKS表达，但不影响应激诱导的膜MARCKS减少。总的来说，这些数据表明，与C57 BL/6 J小鼠相比，DBA/2 J小鼠海马中MARCKS的静息水平更高，并且急性应激导致C57 BL/6 J小鼠和大鼠但不是DBA/2 J小鼠中膜MARCKS表达的长期减少。这些应变海马MARCKS表达和亚细胞易位压力后的差异可能有助于这些菌株之间观察到的行为需要海马可塑性的差异。
The myristoylated alanine‐rich C kinase substrate (MARCKS) is a major protein kinase C (PKC) substrate in brain that binds the inner surface of the plasma membrane, calmodulin, and cross‐links filamentous actin, all in a PKC phosphorylation‐reversible manner. MARCKS has been implicated in hippocampal‐dependent learning and long‐term potentiation (LTP). Previous studies have shown DBA/2 mice to exhibit poor spatial/contextual learning, impaired hippocampal LTP, and hippocampal mossy fiber hypoplasia, as well as reduced hippocampal PKC activity and expression relative to C57BL/6 mice. In the present study, we assessed the expression (mRNA and protein) and subcellular distribution (membrane and cytolsol) of MARCKS in the hippocampus and frontal cortex of C57BL/6 and DBA/2 mice using quantitative western blotting. In the hippocampus, total MARCKS mRNA and protein levels in C57BL/6J mice were significantly lower (∼45%) compared with DBA/2J mice, and MARCKS protein was observed predominantly in the cytosolic fraction. MARCKS expression in frontal cortex did not differ significantly between strains. To examine the dynamic regulation of MARCKS subcellular distribution, mice from each strain were subjected to 60 min restraint stress and MARCKS subcellular distribution was determined 24 h later. Restraint stress resulted in a significant reduction in membrane MARCKS expression in C57BL/6J hippocampus but not in the DBA/2J hippocampus despite similar stress‐induced increases in serum corticosterone. Restraint stress did not affect cytosolic or total MARCKS levels in either strain. Similarly, restraint stress (30 min) in rats also induced a significant reduction in membrane MARCKS, but not total or cytosolic MARCKS, in the hippocampus but not in frontal cortex. In rats, chronic lithium treatment prior to stress exposure reduced hippocampal MARCKS expression but did not affect the stress‐induced reduction in membrane MARCKS. Collectively these data demonstrate higher resting levels of MARCKS in the hippocampus of DBA/2J mice compared to C57BL/6J mice, and that acute stress leads to a long‐term reduction in membrane MARCKS expression in C57BL/6J mice and rats but not in DBA/2J mice. These strain differences in hippocampal MARCKS expression and subcellular translocation following stress may contribute to the differences in behaviors requiring hippocampal plasticity observed between these strains.