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Systems Characterization of Cell Surface Receptors

04.06.2007
Cells communicate with their environment through molecules on their surface known as receptors. Receptors bind ligands - specific companion molecules that either carry information about the outside environment or are critical cell nutrients. A variety of receptors are internalized into the cell through a process known as endocytosis. Receptors display a wide range of state-dependent endocytosis rates, but the functional significance of these patterns is not well understood.

In a paper publishing today (June 1) in the Open Access journal PLoS Computational Biology, Drs. Shankaran, Resat and Wiley from the Pacific Northwest National Laboratory employ a generalized mathematical model to comparatively explore the design principles of signal transduction and transport receptors.

The authors use a new module-based systems theory approach along with quantitative metrics for network function and robustness to show that endocytosis and other receptor/ligand properties can be described by just a few control parameters. Using mathematical analysis, the authors show that the efficiency and robustness of receptor systems are encoded by two fundamental parameters: the avidity which quantifies the ability of a receptor system to capture ligand, and the consumption which quantifies the ability to internalize bound ligand.

By examining a number of receptor systems, the authors demonstrate that the response of receptor systems can be characterized as being: i) avidity-controlled, which depends primarily on ligand capture efficiency, ii) consumption-controlled where the ability to internalize surface-bound ligand is the primary control parameter, and iii) dual-sensitive, in which both the avidity and consumption parameters are important. The location of various receptor systems in control parameter space dictates their specific function and regulation.

... more about:
»Ligand »Receptors »endocytosis »receptor

Most significantly, the authors argue that the evolution of a given receptor system can be understood in terms of its optimal location in avidity-consumption parameter space. For example, induced endocytosis can be shown to be an optimal solution for achieving high fidelity information transmission for signaling receptors. Overall, this study develops and applies a new strategy for quantifying the phenotype of complex systems that should be generally applicable to a wide range of problems in systems biology research.

The research was funded by the National Institutes of Health and the Biomolecular Systems Initiative at PNNL.

Andrew Hyde | alfa
Further information:
http://www.plos.org
http://compbiol.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pcbi.0030101

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