Mammalian glucose transporter activity is dependent upon anionic and conical phospholipids

Richard C. Hresko, Thomas E. Kraft, Andrew Quigley, Elisabeth P. Carpenter, Paul W. Hruz

Research output: Contribution to journalArticle

26 Scopus citations


The regulated movement of glucose across mammalian cell membranes is mediated by facilitative glucose transporters (GLUTs) embedded in lipid bilayers. Despite the known importance of phospholipids in regulating protein structure and activity, the lipid-induced effects on the GLUTs remain poorly understood. We systematically examined the effects of physiologically relevant phospholipids on glucose transport in liposomes containing purified GLUT4 and GLUT3. The anionic phospholipids, phosphatidic acid, phosphatidylserine, phosphatidylglycerol, and phosphatidylinositol, were found to be essential for transporter function by activating it and stabilizing its structure. Conical lipids, phosphatidylethanolamine and diacylglycerol, enhanced transporter activity up to 3-fold in the presence of anionic phospholipids but did not stabilize protein structure. Kinetic analyses revealed that both lipids increase the kcat of transport without changing the Km values. These results allowed us to elucidate the activation of GLUT by plasma membrane phospholipids and to extend the field of membrane protein-lipid interactions to the family of structurally and functionally related human solute carriers.

Original languageEnglish
Pages (from-to)17271-17282
Number of pages12
JournalJournal of Biological Chemistry
Issue number33
StatePublished - Aug 12 2016

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