Researchers have developed an important tool for understanding how one key molecule regulates a wide range of physiological activity in mammals. Using the natural tendency of certain proteins to glow - their fluorescence - research funded in part by the National Science Foundation (NSF) has revealed some surprising variations in how even cells of the same type behave.
Cyclic guanosine monophosphate (cGMP) is a messenger molecule that influences muscle tone, nerve sensitivity, sexual response, vision and learning, among other physiological processes. Understanding cGMP behavior could in turn yield techniques for regulating its positive or negative effects in humans.
The NSF-funded portion of the research was conducted by Wolfgang Dostmann at the University of Vermont. He and University of California, San Diego colleague Roger Tsien - who is funded by the National Institutes of Health and the Howard Hughes Medical Institute - drew on methods from molecular biology, protein/peptide chemistry and cell biology to construct a set of fluorescent indicators named "cygnets," for cyclic GMP indicator using energy transfer.
According to Randolph Addison, program officer in NSF’s Signal Transduction Program, "Dostmann and Tsien ingeniously created genetically encoded indicators that can help us solve fundamental questions such as how cells perceive and respond to other cells."
Until now, cGMP could only be observed invasively, by killing and homogenizing the tissue. Such techniques can yield unreliable results, compared with examining cells in their natural circumstances. The non-invasive cygnet technique, because it allows study of living tissue, is yielding much more detailed and reliable results.
This crucial molecule has been mystifying because it may appear very briefly and in small concentrations within a cell. To be announced in the February 27, 2001 issue of Proceedings of the National Academy of Sciences, Dostmann’s and Tsien’s results demonstrate that, even in cells of the same type, cGMP can appear in widely varying concentrations and will react to stimuli in surprising ways. For instance, some cells respond quickly to stimuli by producing cGMP, while others under the same stimulation may yield no perceptible traces of the molecule.
Still other cells exhibit what appears to be microscopic "tides" of cGMP that travel perceptibly from one side of the cell to another. The researchers created the detector cygnets by sandwiching a cGMP-sensitive protein between two colors of a protein that spontaneously becomes fluorescent when placed in mammalian cells. By using cygnets, biologists may be able to explain fundamental cell behaviors that until now were difficult or impossible to observe.
For an animation of cGMP, see: http://nsf.gov/od/lpa/news/press/01/pr0114.htmFor the Dostmann/Tsien article in Proceedings of the National Academy of Sciences, see: http://www.pnas.org
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