Systems approach to explore components and interactions in the presynapse.

Systems approach to explore components and interactions in the presynapse.
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DOI:
10.1002/pmic.200800767
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发表时间:
2009-06
期刊:
影响因子:
3.4
通讯作者:
Devi, Lakshmi A.
Devi, Lakshmi A.
中科院分区:
生物学3区
文献类型:
--
作者:
Abul-Husn, Noura S.;Bushlin, Ittai;Moron, Jose A.;Jenkins, Sherry L.;Dolios, Georgia;Wang, Rong;Iyengar, Ravi;Ma'ayan, Avi;Devi, Lakshmi A.

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The application of proteomic techniques to neuroscientific research provides an opportunity for a greater understanding of nervous system structure and function. As increasing amounts of neuroproteomic data become available, it is necessary to formulate methods to integrate these data in a meaningful way to obtain a more comprehensive picture of neuronal subcompartments. Furthermore, computational methods can be used to make biologically relevant predictions from large proteomic datasets. Here, we applied an integrated proteomics and systems biology approach to characterize the presynaptic nerve terminal. For this, we carried out proteomic analyses of presynaptically enriched fractions, and generated a presynaptic literature-based protein-protein interaction (PPI) network. We combined these with other proteomic analyses to generate a core list of 117 presynaptic proteins, and used graph theory-inspired algorithms to predict 92 additional components and a presynaptic complex containing 17 proteins. Some of these predictions were validated experimentally, indicating that the computational analyses can identify novel proteins and complexes in a subcellular compartment. We conclude that the combination of techniques (proteomics, data integration, and computational analyses) used in this study are useful in obtaining a comprehensive understanding of functional components, especially low-abundance entities and/or interactions in the presynaptic nerve terminal.
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