Structure of, and functional insight into the GLUT family of membrane transporters

Abstract

This review examines the development of structure and function of the human GLUT proteins, gene family hSLC2A. These proteins are essential for moving the key metabolites, glucose, galactose, and fructose in and out of cells, as well as a number of other important substrates. Despite over five decades of research, it is still not fully understood how they work at the molecular level, although the recent publication of a crystal structure of GLUT1 suggests this may be resolved soon. The GLUT family is divided into three classes based on their sequence homology. The physiological roles of Class I GLUTs, ie, 1, 2, 3 (14), and 4 have been extensively studied for their contributions to metabolism and development. However, the other two classes have received far less attention. Genetic diseases associated with GLUTs are very rare, emphasizing their critical roles, but it is likely that as our understanding of these transporters increases, there may be more clinical conditions found to be associated with subtle changes in their activity. Another promising area of investigation is the changes in expression levels of GLUTs associated with, and likely in consequence of, disease processes. It has long been known that GLUT1 expression increases significantly in cancer cells, but it is now becoming appreciated that other GLUTs may also be involved. Determination of alterations in expression patterns may prove to be a useful diagnostic tool, and in some cases these are already being taken advantage of for the imaging of cancers. Finally, as we better understand how GLUTs bind and transport their substrates, it may be possible to design drugs that can be delivered into target cells for the treatment of a number of diseases.