New Technology Enables Better Understanding of Brain Development
Researchers at Pacific Northwest National Laboratory recently spatially mapped 4,855 neuronal proteins to discover how they connect to complex signaling networks that guide the function of nerve cells (neurons). This effort may lead to enhanced understanding of brain development, neurodegenerative diseases, and spinal cord regeneration.
PNNL researchers worked with team leads at the University of California-San Diego (UCSD) School of Medicine and the Moores UCSD Cancer Center to apply global proteome profiling along with a novel neurite purification technology to enable comparisons of the proteomes of nerve cell bodies (soma) and associated cell projections (neurites). They used quantitative mass spectrometry, computational software, and bioinformatics to match proteins to their cellular functions to better understand the complex signaling mechanisms by which neurites grow into nerve fibers called axons or dendrites, which, respectively, conduct electrical impulses away from or to the soma. This signaling process, which is crucial for proper wiring of the brain and nerve regeneration, has been linked to numerous neurodegenerative diseases, such as Parkinson’s or Alzheimer’s diseases.
Some of this work was conducted in the Environmental Molecular Sciences Laboratory, a DOE national scientific user facility located at PNNL that provides integrated experimental and computational resources for discovery and technological innovation in the environmental molecular sciences to support the needs of the Department of Energy and the nation.
Continuing work includes using PNNL’s advanced capabilities for phosphosproteome analysis to map neurite and soma signal transduction events. To date, more than 3,000 phosphopetides have been identified. Integration of neurite and soma proteome and phosphoproteomes will provide further understanding of the cell signaling process underlying neurodegenerative diseases.
The research team included Dick Smith, Feng Yang, and David Camp, all PNNL, and Richard Klemke, Olivier Pertz, Yingchun Wang, Wei Wang, Laurie J. Gay, UCSD Department of Pathology and Moores UCSD Cancer Center. The work was funded by grants from the National Institutes of Health, the Susan G. Komen Foundation, and a Cell Migration Consortium Grant.
Citation: O.C., Pertz, Y. Wang, F. Yang, W. Wang, L. J. Gay, M. A. Gritsenko, T. R. Clauss, D. J. Anderson, T. Liu, K. J. Auberry, D. G. Camp II, R. D. Smith, R. L. Klemke, 2008, "Spatial Mapping of the Neurite and Soma Proteomes Reveals a Functional Cdc42/Rac Regulatory Network", Proceedings of the National Academy of Science 105: 1931-1936; published online on February 1, 2008, 10.1073/pnas.0706545105