The protein architecture of human secretory vesicles reveals differential regulation of signaling molecule secretion by protein kinases.
The protein architecture of human secretory vesicles reveals differential regulation of signaling molecule secretion by protein kinases.
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DOI：
10.1371/journal.pone.0041134
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Hook V
中科院分区：
文献类型：
--
作者：
Bark SJ;Wegrzyn J;Taupenot L;Ziegler M;O'Connor DT;Ma Q;Smoot M;Ideker T;Hook V
分泌囊泡是释放化学信使以介导人类生物系统中细胞间信号传导所必需的。这是必要的，以确定组织的蛋白质结构的“人”致密核心分泌囊泡（DCSV），以了解机制分泌的信号分子的细胞调控过程中必不可少的。因此，本研究对从人嗜铬细胞瘤中纯化的人DCSV进行了广泛的定量蛋白质组学和系统生物学分析。通过对300多种蛋白质的定量评价，鉴定了600多种人DCSV蛋白质，揭示了大多数蛋白质参与产生肽激素和神经递质、酶和分泌机制。系统生物学分析提供了一个相互作用的DCSV蛋白的模型，产生的差异细胞内蛋白激酶A和C信号通路的假设。细胞PKA和PKC途径的激活导致阿尔茨海默病的神经肽、儿茶酚胺和β-淀粉样蛋白的差异分泌，以介导细胞-细胞通讯。这是第一个定义人类疾病和健康的人类DCSV蛋白质结构模型的研究。
Secretory vesicles are required for release of chemical messengers to mediate intercellular signaling among human biological systems. It is necessary to define the organization of the protein architecture of the ‘human’ dense core secretory vesicles (DCSV) to understand mechanisms for secretion of signaling molecules essential for cellular regulatory processes. This study, therefore, conducted extensive quantitative proteomics and systems biology analyses of human DCSV purified from human pheochromocytoma. Over 600 human DCSV proteins were identified with quantitative evaluation of over 300 proteins, revealing that most proteins participate in producing peptide hormones and neurotransmitters, enzymes, and the secretory machinery. Systems biology analyses provided a model of interacting DCSV proteins, generating hypotheses for differential intracellular protein kinases A and C signaling pathways. Activation of cellular PKA and PKC pathways resulted in differential secretion of neuropeptides, catecholamines, and β-amyloid of Alzheimer's disease for mediating cell-cell communication. This is the first study to define a model of the protein architecture of human DCSV for human disease and health.
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影响因子：
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