Regulation of protein kinase C isozymes during early postnatal hippocampal development.
Regulation of protein kinase C isozymes during early postnatal hippocampal development.
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DOI：
10.1016/j.brainres.2009.06.074
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发表时间：
2009-09-08
期刊：
影响因子：
2.9
通讯作者：
Banerjee P
中科院分区：
文献类型：
--
作者：
Purkayastha S;Fernando SS;Diallo S;Cohen L;Ranasinghe B;Levano K;Banerjee P
在新生儿海马发育期间，5-羟色胺1A受体介导的信号最初使用PKCε促进神经元增殖，然后使用PKCα促进突触发生。PKC同工酶的这种阶段特异性参与可以通过其相对表达水平来确定。在出生后第2-6天（P2-6），我们检测到相对较低水平的α、β、γ和δ同工酶，随后其表达大幅增加。与此相反，PKC同工酶ε和θ在P6时相对丰富，随后它们在P15时进一步增加。与纯化蛋白质的比较证实，P6和P15的PKCε水平分别为1.75和7.36 ng/60 µg蛋白，而P6和P15的PKCα水平分别为160 pg和1.186 ng/60 µg蛋白。因此，在P6，PKC β的丰度比PKCα高约11倍。因此，信号级联可以使用相对丰富的PKCε（可能还有PKCθ）分子在P2-6的早期事件（例如神经发生）中发挥作用，随后PKCα（以及β、γ或δ同工酶）可以指导成熟或凋亡。值得注意的是，在P6而不是P15，PKCε定位于成神经细胞的细胞核，可能指导有丝分裂。而在P15，PKCα在分化的海马神经元突起中呈高表达，而在P6则无表达。总之，PKC同工酶在新生儿海马中的表达差异，每个同工酶的相对丰度可能决定其参与海马发育的模式和阶段。
During neonatal hippocampal development, serotonin 1A receptor-mediated signaling initially employs PKCε to boost neuronal proliferation and then uses PKCα to promote synaptogenesis. Such stage-specific involvement of a PKC isozyme could be determined by its relative expression level. In mouse hippocampi, we detected relatively low levels of α, β, γ, and δ isozymes at post-natal days 2–6 (P2–6), which was followed by a large increase in their expression. In contrast, the PKC isozymes ε and θ were relatively abundant at P6, following which they underwent a further increase by P15. Comparison with purified proteins confirmed that the PKCε levels at P6 and P15 were respectively 1.75 and 7.36 ng per 60 µg of protein, whereas PKCα levels at P6 and P15 were respectively 160 pg and 1.186 ng per 60 µg of protein. Therefore, at P6, PKCepsilon was about 11-fold more abundant than PKCα. Consequently, signaling cascades could use the relatively abundant PKCε (and possibly PKCθ) molecules for early events at P2-6 (e.g. neurogenesis), following which PKCα (and the β, γ, or δ isozymes) could guide maturation or apoptosis. Notably, at P6 but not P15, PKCε, was localized to the nuclei of neuroblasts, probably directing mitosis. In contrast, at P15 but not P6, PKCα was highly expressed in the processes of the differentiated hippocampal neurons. In summary, PKC isozymes follow differential profiles of expression in neonatal hippocampus and the relative abundance of each may determine its mode and stage of involvement in hippocampal development.
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