First Comprehensive Profile of Cell Movement Created by PNNL, UCSD
Combined proteomics and phosphoproteomics approaches make it possible
Results: Scientists at Pacific Northwest National Laboratory and the University of California, San Diego have created the first comprehensive profile of cell movement. They mapped an extensive network of the signaling proteins controlling cell movement. Their work was published May 15 in Proceedings of the National Academy of Sciences (PNAS). UCSD published a news release entitled "How to Steer a Moving Cell." The work was also highlighted in the Editors' Choice section in the online journal Science STKE (Signal Transduction Kinase Expression).
Methods: The PNNL team applied global proteome profiling in combination with UCSD-developed phosphoproteomics approaches to understand signal organization in migrating cells. The scientists developed a system that facilitates the separation and isolation of the pseudopodium (PD, or leading part of the cell) and the cell body (CB) compartments of chemotaxing cells for proteomic analysis using microporous filters. This model system recapitulates physiological events associated with chemotaxis including gradient sensing and pseudopodial protrusion through small openings in the vessel wall during cancer cell metastasis. They mapped the spatial relationship of 3,509 proteins and 225 distinct phosphorylation sites. This revealed networks of signaling proteins that are partitioned into the PD and/or the CB compartments.
Why It Matters: This knowledge could lead to a better understanding of cell migration in cancer metastasis and inflammatory disease, which in turn will help in the development of effective treatment methods.
This figure represents the microporous filter system for purification and mass spectrometry analysis of PD and CB fractions isolated from polarized cells. It depicts the comparative characterization of the entire cellular movement model. Enlarged View
What's Next: Future work to integrate the PD proteome and phosphoproteomes with genomic and proteomic databases will provide a novel approach for developing diagnostics for cancer and immune disorders.
Acknowledgments: The research team includes Richard Klemke and Wei Wang, UCSD School of Medicine, and Shi-Jian Ding, Jon Jacobs, Wei-Jun Qian, Ron Moore, Feng Yang, Dave Camp, and Dick Smith at PNNL. Funding was provided by the Susan G. Komen Foundation, the National Institutes of Health, the Cell Migration Consortium, and Laboratory Directed Research and Development at PNNL. The work at PNNL was performed at the Environmental Molecular Sciences Laboratory, a U.S. Department of Energy national scientific user facility.
Reference: Wang Y, SJ Ding, W Wang, JM Jacobs, WJ Qian, RJ Moore, F Yang, DG Camp II, RD Smith, and RL Klemke. 2007. "Profiling signaling polarity in chemotactic cells." Proceedings of the National Academy of Sciences 104(20):8328-8333 doi 10.1073/pnas.0701103104.