GLUT1

Uniporter protein

Glucose transporter 1 (or GLUT1), also known as solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1), is a uniporter protein that in humans is encoded by the SLC2A1 gene. GLUT1 facilitates the transport of glucose across the plasma membranes of mammalian cells. This gene encodes a facilitative glucose transporter that is highly expressed in erythrocytes and endothelial cells, including cells of the blood–brain barrier. The encoded protein is found primarily in the cell membrane and on the cell surface, where it can also function as a receptor for human T cell leukemia virus (HTLV) I and II. GLUT1 accounts for 2 percent of the protein in the plasma membrane of erythrocytes. Mutations in this gene can cause GLUT1 deficiency syndrome 1, GLUT1 deficiency syndrome 2, idiopathic generalized epilepsy 12, dystonia 9, and stomatin deficient cryohydrocytosis.

GLUT1 was the first glucose transporter to be characterized. GLUT 1 is highly conserved.

The SLC2A1 gene is located on the p arm of chromosome 1 in position 34.2 and has 10 exons spanning 33,802 base pairs. It is a multi pass protein located in the cell membrane. GLUT1 is responsible for the low level of basal glucose uptake required to sustain respiration in all cells. Expression levels of GLUT1 in cell membranes are increased by reduced glucose levels and decreased by increased glucose levels. GLUT1 is also a major receptor for uptake of Vitamin C as well as glucose, especially in non vitamin C producing mammals as part of an adaptation to compensate by participating in a Vitamin C recycling process. In mammals that do produce Vitamin C, GLUT4 is often expressed instead of GLUT1.

GLUT1 expression occurs in almost all tissues, with the degree of expression typically correlating with the rate of cellular glucose metabolism. In the adult it is expressed at highest levels in erythrocytes and also in the endothelial cells of barrier tissues such as the blood–brain barrier.

Mutations in the GLUT1 gene are responsible for GLUT1 deficiency or De Vivo disease, which is a rare autosomal dominant disorder. This disease is characterized by a low cerebrospinal fluid glucose concentration (hypoglycorrhachia), a type of neuroglycopenia, which results from impaired glucose transport across the blood–brain barrier.

Many mutations in the SLC2A1 gene, including LYS456TER, TYR449TER, LYS256VAL, ARG126HIS, ARG126LEU and GLY91ASP, have been shown to cause GLUT1 deficiency syndrome 1 (GLUT1DS1), a neurologic disorder showing wide phenotypic variability. This disease can be inherited in either an autosomal recessive or autosomal dominant manner.

GLUT1 has been shown to interact with GIPC1. It is found in a complex with Adducin (ADD2) and Dematin (EPB49) and interacts (via C terminus cytoplasmic region) with Dematin isoform 2. It also interacts with SNX27; the interaction is required when endocytosed to prevent degradation in lysosomes and promote recycling to the plasma membrane. This protein interacts with STOM. It interacts with SGTA (via Gln rich region) and has binary interactions with CREB3 2.

Fasentin is a small molecule inhibitor of the intracellular domain of GLUT1 preventing glucose uptake. Recently, a new more selective GLUT1 inhibitor, Bay 876, has been described.