Role of lipid polymorphism in G protein-membrane interactions: nonlamellar-prone phospholipids and peripheral protein binding to membranes.
Heterotrimeric G proteins (peripheral proteins) conduct signals from membrane receptors (integral proteins) to regulatory proteins localized to various cellular compartments. They are in excess over any G protein-coupled receptor type on the cell membrane, which is necessary for signal amplification. These facts account for the large number of G protein molecules bound to membrane lipids. Thus, the protein-lipid interactions are crucial for their cellular localization, and consequently for signal transduction. In this work, the binding of G protein subunits to model membranes (liposomes), formed with defined membrane lipids, has been studied. It is shown that although G protein alpha-subunits were able to bind to lipid bilayers, the presence of nonlamellar-prone phospholipids (phosphatidylethanolamines) enhanced their binding to model membranes. This mechanism also appears to be used by other (structurally and functionally unrelated) peripheral proteins, such as protein kinase C and the insect protein apolipophorin III, indicating that it could constitute a general mode of protein-lipid interactions, relevant in the activity and translocation of some peripheral (amphitropic) proteins from soluble to particulate compartments. Other factors, such as the presence of cholesterol or the vesicle surface charge, also modulated the binding of the G protein subunits to lipid bilayers. Conversely, the binding of G protein-coupled receptor kinase 2 and the G protein beta-subunit to liposomes was not increased by hexagonally prone lipids. Their distinct interactions with membrane lipids may, in part, explain the different cellular localizations of all of these proteins during the signaling process.
Escribá
P V
PV
Laboratory of Neuropharmacology, Department of Biology, University of the Balearic Islands, E-07071 Palma de Mallorca, Spain.
Ozaita
A
A
Ribas
C
C
Miralles
A
A
Fodor
E
E
Farkas
T
T
García-Sevilla
J A
JA
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008081:Liposomes; D046911:Macromolecular Substances; D008563:Membrane Lipids / Q000378:metabolism*; D008954:Models, Biological; D010743:Phospholipids / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D008081:Liposomes; D046911:Macromolecular Substances; D008563:Membrane Lipids; D010743:Phospholipids; D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins