Lipid-protein interactions in GPCR-associated signaling.
Signal transduction via G-protein-coupled receptors (GPCRs) is a fundamental pathway through which the functions of an individual cell can be integrated within the demands of a multicellular organism. Since this family of receptors first discovered, the proteins that constitute this signaling cascade and their interactions with one another have been studied intensely. In parallel, the pivotal role of lipids in the correct and efficient propagation of extracellular signals has attracted ever increasing attention. This is not surprising given that most of the signal transduction machinery is membrane-associated and therefore lipid-related. Hence, lipid-protein interactions exert a considerable influence on the activity of these proteins. This review focuses on the post-translational lipid modifications of GPCRs and G proteins (palmitoylation, myristoylation, and isoprenylation) and their significance for membrane binding, trafficking and signaling. Moreover, we address how the particular biophysical properties of different membrane structures may regulate the localization of these proteins and the potential functional consequences of this phenomenon in signal transduction. Finally, the interactions that occur between membrane lipids and GPCR effector enzymes such as PLC and PKC are also considered.
Escribá
Pablo V
PV
Laboratory of Molecular and Cellular Biomedicine, Institut Universitari d'Investigació en Ciències de la Salut, Department of Biology, University of the Balearic Islands, Palma de Mallorca, Spain. pablo.escriba@uib.es
Wedegaertner
Philip B
PB
Goñi
Félix M
FM
Vögler
Oliver
O
D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction
D008563:Membrane Lipids; D043562:Receptors, G-Protein-Coupled; D020962:Heterotrimeric GTP-Binding Proteins