title: G protein-membrane interactions I: Gαi1 myristoyl and palmitoyl modifications in protein-lipid interactions and its implications in membrane microdomain localization.
abstract: 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 Gαi1 protein with model and biological membranes. For this purpose, we quantified the binding of purified Gαi1 protein and Gαi1 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 Gαi1 subunit interaction with lipids characteristics of certain membrane microdomains. Thus, when the Gαi1 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 Gαi1 subunit prefers other types of ordered lipid microdomains with higher phosphatidylserine content. These results in part explain the mobility of Gαi1 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.
authors.affiliation: Laboratory of Molecular Cell Biomedicine, Department of Biology, IUNICS, University of Islas Baleares, Carretera de Valldemossa km 7.5, E-07122 Palma de Mallorca, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Álvarez
authors.affiliation: Laboratory of Molecular Cell Biomedicine, Department of Biology, IUNICS, University of Islas Baleares, Carretera de Valldemossa km 7.5, E-07122 Palma de Mallorca, Spain.
authors.forename: David J
authors.initials: DJ
authors.lastname: López
authors.affiliation: Laboratory of Molecular Cell Biomedicine, Department of Biology, IUNICS, University of Islas Baleares, Carretera de Valldemossa km 7.5, E-07122 Palma de Mallorca, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Casas
authors.affiliation: Laboratory of Molecular Cell Biomedicine, Department of Biology, IUNICS, University of Islas Baleares, Carretera de Valldemossa km 7.5, E-07122 Palma de Mallorca, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Lladó
authors.affiliation: Laboratory of Molecular Cell Biomedicine, Department of Biology, IUNICS, University of Islas Baleares, Carretera de Valldemossa km 7.5, E-07122 Palma de Mallorca, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Higuera
authors.affiliation: Laboratory of Molecular Cell Biomedicine, Department of Biology, IUNICS, University of Islas Baleares, Carretera de Valldemossa km 7.5, E-07122 Palma de Mallorca, Spain.
authors.forename: Tünde
authors.initials: T
authors.lastname: Nagy
authors.affiliation: Bioinorganic and Bioorganic Research Group, Department of Chemistry, IUNICS, University of Islas Baleares, Carretera de Valldemossa km 7.5, E-07122 Palma de Mallorca, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Barceló
authors.affiliation: Laboratory of Molecular Cell Biomedicine, Department of Biology, IUNICS, University of Islas Baleares, Carretera de Valldemossa km 7.5, E-07122 Palma de Mallorca, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Busquets
authors.affiliation: Laboratory of Molecular Cell Biomedicine, Department of Biology, IUNICS, University of Islas Baleares, Carretera de Valldemossa km 7.5, E-07122 Palma de Mallorca, Spain. Electronic address: pablo.escriba@uib.es.
authors.forename: Pablo V
authors.initials: PV
authors.lastname: Escribá
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism; D017124:Conserved Sequence; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D054878:Lipoylation; D021962:Membrane Microdomains; D008969:Molecular Sequence Data; D009227:Myristic Acids / Q000737:chemistry / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000737:chemistry / Q000378:metabolism; D010718:Phosphatidylserines / Q000737:chemistry / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D061987:Sf9 Cells; D015398:Signal Transduction; D013109:Sphingomyelins / Q000737:chemistry / Q000378:metabolism; D018411:Spodoptera
chemical_list: C522851:Gnai1 protein, rat; D009227:Myristic Acids; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; D011993:Recombinant Fusion Proteins; D013109:Sphingomyelins; C483858:phosphatidylethanolamine; D002784:Cholesterol; D019206:GTP-Binding Protein alpha Subunits, Gi-Go
keywords: Cell signaling; G protein–lipid interactions; Lipid structure; Membrane microdomain; Myristoylation; Palmitoylation