Yakovleva Tatiana, Bazov Igor, Cebers Gvido, Marinova Zoya, Hara Yuko, Ahmed Aisha, Vlaskovska Mila, Johansson Björn, Hochgeschwender Ute, Singh Indrapal N, Bruce-Keller Annadora J, Hurd Yasmin L, Kaneko Takeshi, Terenius Lars, Ekström Tomas J, Hauser Kurt F, Pickel Virginia M, Bakalkin Georgy
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
FASEB J. 2006 Oct;20(12):2124-6. doi: 10.1096/fj.06-6174fje. Epub 2006 Sep 11.
The classical view postulates that neuropeptide precursors in neurons are processed into mature neuropeptides in the somatic trans-Golgi network (TGN) and in secretory vesicles during axonal transport. Here we show that prodynorphin (PDYN), precursor to dynorphin opioid peptides, is predominantly located in axon terminals and dendrites in hippocampal and striatal neurons. The molar content of unprocessed PDYN was much greater than that of dynorphin peptides in axon terminals of PDYN-containing neurons projecting to the CA3 region of the hippocampus and in the striatal projections to the ventral tegmental area. Electron microscopy showed coexistence of PDYN and dynorphins in the same axon terminals with occasional codistribution in individual dense core vesicles. Thus, the precursor protein is apparently stored at presynaptic sites. In comparison with the hippocampus and striatum, PDYN and dynorphins were more equally distributed between neuronal somata and processes in the amygdala and cerebral cortex, suggesting regional differences in the regulation of trafficking and processing of the precursor protein. Potassium-induced depolarization activated PDYN processing and secretion of opioid peptides in neuronal cultures and in a model cell line. Regulation of PDYN storage and processing at synapses by neuronal activity or extracellular stimuli may provide a local mechanism for regulation of synaptic transmission.
传统观点认为，神经元中的神经肽前体在轴突运输过程中，于体细胞反式高尔基体网络（TGN）和分泌小泡中被加工成成熟的神经肽。在此我们表明，强啡肽阿片肽的前体前强啡肽（PDYN）主要位于海马体和纹状体神经元的轴突终末和树突中。在投射至海马体CA3区的含PDYN神经元的轴突终末以及投射至腹侧被盖区的纹状体投射中，未加工的PDYN的摩尔含量远高于强啡肽肽的摩尔含量。电子显微镜显示，PDYN和强啡肽在同一轴突终末中共存，偶尔在单个致密核心小泡中共同分布。因此，前体蛋白显然储存在突触前位点。与海马体和纹状体相比，PDYN和强啡肽在杏仁核和大脑皮层的神经元胞体和突起之间分布更为均匀，这表明前体蛋白在运输和加工调节方面存在区域差异。钾离子诱导的去极化激活了神经元培养物和模型细胞系中PDYN的加工以及阿片肽的分泌。神经元活动或细胞外刺激对突触处PDYN储存和加工的调节可能为突触传递调节提供一种局部机制。
