One of the most important problems in biomedical reserach is understanding how membrane receptors operate to control the activities of a cell. In multicellular organisms the stimuli are hormones and neurotransmittors; in single celled species, they are indicators of nutritive or deleterious conditions. Although stimuli and responses vary, the underlying molecular mechanisms seem to be similar. Membrane receptor proteins bind chemoeffectors at the extracellular surface. The receptors interact with a set of auxiliary cytoplasmic proteins which process the information they have received and activate appropriate response mechanisms. In recent years considerable progress has been achieved in the isolation and characterization of membrane receptor proteins. Much less is known of the sensory processing mechanisms which mediate their action. In the proposed research, the sensory mechanism which mediates the chemotaxis response of enteric bacteria will be sutdied as a model system to understand general biochemical principles of sensory processing. the interplay between mutagenesis and selection in the development of variant sensory processing strategies will be investigated with an emphasis on determining whether specific mutational mechanisms operate to fine tune the chemotaxis system to a particular environmental setting. Genetic results indicate that two cytoplasmic proteins (the products of the cheY and cheZ genes) play central roles in chemotactic sensory processing. Immunoassays have been developed for Y and Z, and these procedures will be used to isolate the proteins, measure their levels, and probe for their functions. These protocols will be coupled to high resolution chromatographic techniques to elucidate the chemistry of the system which mediates the flow of information between receptors and flagella motor components. Methylation reactions have long been known to play a key role in higher sensory systems. Preliminary results indicate that Y and Z participate in a variety of methylation events. The chemotaxis system provides an ideal experimental setting to investigate the chemistry and function of methyl transfer reactions in sensory processing
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