Systems approach to explore components and interactions in the presynapse
Year: 2009
Type: article
Abstract: 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 data sets. Here, we applied an integrated proteomics and systems biology approach to characterize the presynaptic (PRE) nerve terminal. For this, we carried out proteomic analyses of presynaptically enriched fractions, and generated a PRE literature-based protein-protein interaction network. We combined these with other proteomic analyses to generate a core list of 117 PRE proteins, and used graph theory-inspired algorithms to predict 92 additional components and a PRE 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 PRE nerve terminal.
Source: PROTEOMICS
Institution: Icahn School of Medicine at Mount Sinai
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: National Institute on Drug Abuse, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Center for Research Resources, Lauku atbalsta dienests
Awards: G1008381163, Structure and Function of Signal Transducing Components, THE NINDS MASS SPECTROMETRY PROTEOMICS CENTER FOR NEUROSCIENCES AT MSSM, Natl Resource for Mass Spectrom of Biolog Macromolecules, ENZYMES INVOLVED IN DYNORPHIN BIOSYNTHESIS, Assay to Screen Ligands:Activate Opioid Receptor (RMI), G3328913778, Interdisciplinary Training in Drug Abuse Research, 40th Annual International Narcotics Research Conference, POST-TRANSLATIONAL REGULATION OF OPIOID RECEPTORS, Post-translational Regulation of Opioid Receptors, Functions of Regulatory Motifs in Signaling Networks, 39th Annual International Narcotics Research Conference, Enzymes Involved in Neuropeptide Biosynthesis, Processing and Regulation, Post-translational regulation of opioid receptors, Advanced Microscopy Shared Resource Facility, System Biology Center in New York, Post-translational regulation of opioid and cannabinoid receptors, ProteomeX LTQ Workstation Shared Instrumentation, MASS SPECTROMETRY SHARED RESOURCE, G7872391481, MALD/ESI-Q-TOF Mass Spectrometer Shared Instrument, Regulation Of Opioid Receptor Signaling by Endogenous Peptides
OpenAlex ID: W2012129116