Analysis of mouse brain peptides using mass spectrometry-based peptidomics: implications for novel functions ranging from non-classical neuropeptides to microproteins.
Analysis of mouse brain peptides using mass spectrometry-based peptidomics: implications for novel functions ranging from non-classical neuropeptides to microproteins.
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DOI：
10.1039/c003317k
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发表时间：
2010-08
影响因子：
--
通讯作者：
Fricker LD
中科院分区：
文献类型：
--
作者：
Fricker LD
众所周知，肽在信号传导中发挥着许多重要的生理作用。利用质谱为基础的肽组学研究已在小鼠脑提取物中检测到大量肽，并已鉴定出850个肽。这些肽中有一半来源于分泌途径蛋白，许多是已知的激活G蛋白偶联受体的生物活性神经肽；这些被称为“经典神经肽”。此外，鉴定出427个肽来源于非分泌途径蛋白；多数为囊胞蛋白，其余为线粒体蛋白、核蛋白、溶酶体蛋白或膜蛋白。许多这些肽代表蛋白质的N端或c端，而不是内部片段，这提高了它们是通过选择性加工而不是蛋白质降解形成的可能性。除了考虑产生细胞内肽所需的裂解位点外，还讨论了它们的潜在功能。先前发现一些胞质肽与受体相互作用和/或以其他方式影响细胞活性；例子包括血友病、加压素、地西泮结合抑制剂和海马胆碱能神经刺激肽。讨论了这些肽从细胞分泌并在细胞-细胞信号传导中起作用的可能性。如果这些细胞内多肽的分泌水平足以产生生物效应，它们将被恰当地称为“非经典神经肽”，与非经典神经递质（如一氧化氮和阿南达胺）类似。也有可能细胞内肽作为“微蛋白”起作用并调节蛋白质之间的相互作用；讨论了这种功能的证据，以及建立这种功能和其他可能的肽功能所需的未来方向。
Peptides are known to play many important physiological roles in signaling. A large number of peptides have been detected in mouse brain extracts using mass spectrometry-based peptidomics studies, and 850 peptides have been identified. Half of these peptides are derived from secretory pathway proteins and many are known bioactive neuropeptides which activate G protein-coupled receptors; these are termed “classical neuropeptides.” In addition, 427 peptides were identified that are derived from non-secretory pathway proteins; the majority are cystosolic, and the remainder are mitochondrial, nuclear, lysosomal, or membrane proteins. Many of these peptides represent the N- or C-terminus of the protein, rather than internal fragments, raising the possibility that they are formed by selective processing rather than protein degradation. In addition to consideration of the cleavage site required to generate the intracellular peptides, their potential functions are discussed. Several of the cytosolic peptides were previously found to interact with receptors and/or otherwise influence cellular activity; examples include hemophins, hemopressins, diazepam binding inhibitor, and hippocampal cholinergic neurostimulating peptide. The possibility that these peptides are secreted from cells and function in cell-cell signaling is discussed. If these intracellular peptides can be shown to be secreted in levels sufficient to produce a biological effect, they would appropriately be called “non-classical neuropeptides” by analogy with non-classical neurotransmitters such as nitric oxide and anandamide. It is also possible that intracellular peptides function as “microproteins” and modulate protein-protein interactions; evidence for this function is discussed, along with future directions that are needed to establish this and other possible functions for peptides.
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DOI：
10.1073/pnas.0813216106
发表时间：
2009-09-08
影响因子：
11.1
作者：
Biagioli, Marta;Pinto, Milena;Gustincich, Stefano
通讯作者：
Gustincich, Stefano
影响因子：
4.8
作者：
Che, FY;Yuan, Q;Fricker, LD
通讯作者：
Fricker, LD
影响因子：
2.3
作者：
Baggerman, G;Boonen, K;Schoofs, L
通讯作者：
Schoofs, L
影响因子：
4.8
作者：
Albiston, AL;McDowall, SG;Chai, SY
通讯作者：
Chai, SY
影响因子：
3.4
作者：
BLANKS, JC;SPEE, C
通讯作者：
SPEE, C