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J Biol Chem. 2016 Aug 12;291(33):17271-82. doi: 10.1074/jbc.M116.730168. Epub 2016 Jun 14.

Mammalian Glucose Transporter Activity Is Dependent upon Anionic and Conical Phospholipids.

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From the Departments of Pediatrics and.
From the Departments of Pediatrics and
the Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, United Kingdom.
From the Departments of Pediatrics and Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110 and


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.


glucose transport; glucose transport kinetics; glucose transporter type 3 (GLUT3); glucose transporter type 4 (GLUT4); liposome; membrane transporter reconstitution; phospholipid; phospholipid vesicle; protein-lipid interaction

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