Session 6: Signal transduction in the light membrane structure
What is the influence of membrane lipids on receptor signalling?
Burton Litman
Biological membranes are composed of a great diversity of lipid classes and molecular species within each class. These lipids provide the solvent milieu in which membrane-localized receptors function. The effect of lipid composition can be manifested at several different levels. The biophysical properties of the local environment around a receptor will affect the energetics of receptor conformation changes, which in turn influences ligand binding and the level of receptor activation. These properties will also govern the kinetics and efficiency of the diffusional coupling of components of signalling pathways. An example of this is the effect of the change in lipid composition in the retina in response to a dietary deficiency of n-3 fatty acids, which results in inhibitory changes in several steps of G-protein-coupled receptor signalling in the visual transduction pathway.
Lateral domains or rafts can serve to selectively enrich membranes in specific lipid species in the local environment of a receptor or signalling pathway. In this manner, membrane lipid composition can function as a modulator of receptor and signalling pathway function. Lateral domain or raft formation can also serve to enrich the receptor environment in second messenger precursors, such as phosphoinositides, thereby increasing the concentration of second messengers and enhancing the pathway response to a stimulus. Signalling efficiency can also be enhanced by the partitioning of pathway components within lateral domains or rafts.
Further reading
Eroglu, C., Brugger, B., Wieland, F. & Sinning, I. Glutamate-binding affinity of Drosophila metabotropic glutamate receptor is modulated by association with lipid rafts. Proc. Natl Acad. Sci. 100, 10219-10224 (2003)
Mitchell, D. C & Litman, B. J. in Fatty Acids: From Neuronal Membrane to Physiological and Behavioral Function (eds. Mostofsky, D., Yehuda, S. & Salem, N. Jr.) Ch. 2 (Humana, New Jersey, 2000)
Niu, S. L. et al. Reduced G protein-coupled signaling efficiency in retinal rod outer segments in response to n-3 fatty acid deficiency. J. Biol. Chem. 279, 31098-31104 (2004)
Pike, L. J. Lipid rafts: bringing order to chaos. J. Lipid Res. 44, 655-667 (2003)
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