A presynaptic role for protein kinase C in hippocampal mossy fiber synaptic transmission.
A presynaptic role for protein kinase C in hippocampal mossy fiber synaptic transmission.
复制标题
蛋白激酶 C 在海马苔藓纤维突触传递中的突触前作用。
DOI：
10.1002/hipo.450010321
复制
发表时间：
1991
期刊：
影响因子：
3.5
通讯作者：
Gannon,RL
中科院分区：
文献类型：
--
作者：
Terrian,DM;Ways,DK;Gannon,RL
有研究表明，海马苔藓纤维（MF）突触的长期增强（LTP）的维持涉及一种突触前机制，该机制不需要激活蛋白激酶C (PKC)，因为这种酶在MF突触前末端似乎不存在。在本研究中，作者通过直接比较海马MF突触体和从同一海马组织制备的常规P2B突触体的代谢特性来评估这一提议。蛋白激酶C依赖性组蛋白磷酸转移酶活性在MF和P2B突触体中具有可比性。使用针对四种PKC亚型制备的抗血清进行Western blot分析，结果表明，α， β和γ PKC亚型在这两种亚细胞组分中存在相对相等的量。然而，与P2B突触体制备相比，海马MF突触体的胞质组分似乎含有更多的PKC−∈同种异构体。MF突触体中存在的四种不同的内源性底物被证明在PKC激活的反应中被磷酸化。PKC在海马MF神经末梢的功能作用似乎是通过发现4β - phorbol 12,13 - dibutyrate （PDBu）和4β - phorbol 12,13 - diacetate产生剂量依赖性的内源性谷氨酸和dynorphin B的释放增强，而无活性的4 - α - phorbol没有作用。PDBu诱导的递质释放增强被PKC抑制剂staurosporine阻断。此外，PDBu显著促进了MF突触体膜去极化后胞质游离钙的增加。由此可见，海马MF突触前终末具有多种PKC亚型，其激活可能对MF突触的传递和可塑性具有重要的便利影响。
It has been suggested that the maintenance of long‐term potentiation (LTP) in the hippocampal mossy fiber (MF) synapse involves a presynaptic mechanism that does not require the activation of protein kinase C (PKC), since this enzyme appears to be absent in the MF presynaptic terminals. In the present study the authors evaluated this proposal by directly comparing the metabolic properties of hippocampal MF synaptosomes and a conventional P2B synaptosomes preparation prepared from the same hippocampal tissue. Protein kinase C‐dependent histone phosphotransferase activity was found to be comparable in MF and P2B synaptosomes. Western blot analysis was performed using antisera prepared against four of the PKC isoforms, and the results demonstrate that the α, β, and γ PKC isoforms are present in relatively equivalent amounts in these two subcellular fractions. However, the cytosolic fraction derived from the hippocampal MF synaptosomes appeared to contain a greater amount of the PKC−∈isoform when compared to the P2B synaptosomal preparation. Four distinct endogenous substrates present in the MF synaptosomes are shown to be phosphorylated in response to PKC activation. A functional role for PKC in the hippocampal MF nerve endings seems to be indicated by the finding that 4β‐phorbol 12, 13‐dibutyrate (PDBu) and 4β‐phorbol 12, 13‐diacetate produce a dosedependent potentiation of the K+‐evoked release of endogenous glutamate and dynorphin B, while the inactive 4‐α‐phorbol was without effect. The PDBu‐induced enhancement of transmitter release was blocked by the PKC inhibitor, staurosporine. In addition, PDBu significantly facilitated the rise in cytosolic free calcium that immediately followed depolarization of the MF synaptosomal membrane. It is concluded that hippocampal MF presynaptic terminals possess a variety of PKC isoforms and that their activation may have an important facilitory influence on MF synaptic transmission and plasticity.