Blood-brain barrier glucose transporter is asymmetrically distributed on brain capillary endothelial lumenal and ablumenal membranes: an electron microscopic immunogold study.
It is generally assumed that there is symmetric distribution of the glucose transporter on the lumenal and ablumenal membranes of the brain capillary endothelial cell that makes up the blood-brain barrier (BBB) in vivo. However, the presence of brain endothelial tight junctions allows for asymmetric distribution of BBB plasma membrane proteins. Glucose transporter isoform 1 (GLUT-1), the principal glucose transporter at the BBB, was assessed in rat brain in the present studies using immunogold electron microscopy. The distribution of the immunoreactive GLUT-1 protein on the endothelial lumenal membrane, the ablumenal membrane, and the cytoplasmic compartment was 12%, 48%, and 40%, respectively, and no significant immunolabeling of the neuropil was measurable. These studies suggest (i) that GLUT-1 is asymmetrically distributed on the BBB plasma membrane with an approximately 4-fold greater abundance on the ablumenal membrane as compared to the lumenal membrane; (ii) that approximately 40% of the endothelial glucose transporter protein is contained within the cytoplasmic space, which provides a mechanism for rapid up-regulation of the transporter by altered distribution of transporter between cytoplasmic and plasma membrane compartments; and (iii) that no significant labeling of neuropil is found with antisera directed against the GLUT-1 protein. These studies also suggest mechanisms of regulation of glucose transport from blood to brain that involve differential distribution of the BBB glucose transporter in subcellular compartments of brain capillary endothelial cells.