G protein-membrane interactions I: Gαi1 myristoyl and palmitoyl modifications in protein-lipid interactions and its implications in membrane microdomain localization

G proteins are fundamental elements in signal transduction involved in key cell responses, and their interactions with cell membrane lipids are critical events whose nature is not fully understood. Here, we have studied how the presence of myristic and palmitic acid moieties affects the interaction of the Gull protein with model and biological membranes. For this purpose, we quantified the binding of purified G alpha i(1) protein and G alpha i(1) protein acylation mutants to model membranes, with lipid compositions that resemble different membrane microdomains. We observed that myristic and palmitic acids not only act as membrane anchors but also regulate G alpha i(1) subunit interaction with lipids characteristics of certain membrane microdomains. Thus, when the G alpha i(1) subunit contains both fatty acids it prefers raft-like lamellar membranes, with a high sphingomyelin and cholesterol content and little phosphatidylserine and phosphatidylethanolamine. By contrast, the myristoylated and non-palmitoylated subunit prefers other types of ordered lipid microdomains with higher phosphatidylserine content These results in part explain the mobility of G alpha i(1) protein upon reversible palmitoylation to meet one or another type of signaling protein partner. These results also serve as an example of how membrane lipid alterations can change membrane signaling or how membrane lipid therapy can regulate the cell's physiology. (C) 2015 Published by Elsevier B.V.