Dean of the Graduate School of Biomedical Sciences
Tony Carruthers received his B.Sc. degree from the University of Manchester (U.K.) in 1977 and his Ph.D.in cellular physiology from King's College, London, in 1980. In 1982 he received a Wellcome Trust Travel Award and a NATO Overseas Postdoctoral Fellowship to perform postdoctoral work at the University of Massachusetts Medical Center.
Following his postdoctoral work, he remained at UMass Medical School as a faculty member in the Department of Biochemistry and Molecular Pharmacology.
Research in my laboratory is aimed at understanding protein-mediated transport of nutrients and other small molecules across cell membranes.
The Major Facilitator Superfamily (MFS) of transport proteins comprises more than 1,000 unique proteins that mediate passive and secondary active transmembrane transport of nutrients, drugs, ions, neurotransmitters, and other molecules in all organisms. The facilitative glucose transporter family (GLUT or SLC2A) mediates the uniport of monosaccharides and other small molecules in vertebrates. GLUT proteins are expressed in an organ-system specific manner allowing them to meet the metabolic needs of the organism. For example, GLUT2 is found in the liver and glucose sensing cells of the CNS, GLUT3 is expressed in neuronal cells, and insulin-sensitive GLUT4 is found in muscle and adipose tissue. GLUT1 is found in many tissues throughout the body but is expressed most highly in CNS astrocytes, in β-cells of the human pancreas, in the circulatory system and at blood-tissue barriers such as the blood-brain barrier where it mediates glucose transfer from blood to brain. The focus of our laboratory is to understand the molecular basis of GLUT function and regulation.
Our methods include molecular biology, genetics, protein chemistry, mass spectrometry, biochemistry, biophysics and cellular physiology. More details about the laboratory may be found at our lab web page http://glutxi.umassmed.edu/index.html
Ultrastructure of Human Erythrocyte GLUT1
Analysis of GLUT1 aggregation state by freeze-fracture electron microscopy. High magnification of unidirectionally shadowed freeze-fractured electron micrographs of GLUT1 proteoliposomes. Composite of nonreduced (left) and reduced (middle), purified GLUT1 Integral Membrane Particles. The bar represents 10 nm. The images represent the average of 60 particles. The rightmost image shows the dimensions of monomeric GLUT1 threaded through GlpT structure.
Structural basis of GLUT1 regulation by ATP
ATP regulation of GLUT1. GLUT1 membrane spanning topography is illustrated. GLUT1 behavior is illustrated in the presence of AMP (left) or ATP (right). Trypsin cleavage sites (yellow and brown circles), sites of antibody recognition (green and red sequence), and sites where IgG binding is not detected (blue sequence) are indicated. In the presence of ATP (right), ATP-sensitive (red sequence) and insensitive (green sequence) IgG binding domains are also indicated. The circles show ATP-insensitive tryptic cleavage sites (yellow circles), ATP-protected tryptic cleavage sites (brown circles), and ATP-protected sites of lysine covalent modification by Sulfo-NHS-LC-Biotin (red circles). We propose that the GLUT1 C-terminus and the C-terminal half of the middle loop interact in response to ATP binding. This reduces their respective accessibility to polar reagents and restricts glucose release from the translocation pathway.