Facilitative glucose transporter Glut1 is actively excluded from rod outer segments

Abstract

SummaryPhotoreceptors are among the most metabolically active cells in the body, relying on both oxidative phosphorylation and glycolysis to satisfy their high energy needs. Local glycolysis is thought to be particularly crucial in supporting the function of the photoreceptor's light-sensitive outer segment compartment, which is devoid of mitochondria. Accordingly, it has been commonly accepted that the facilitative glucose transporter Glut1 responsible for glucose entry into photoreceptors is localized in part to the outer segment plasma membrane. However, we now demonstrate that Glut1 is entirely absent from the rod outer segment and is actively excluded from this compartment by targeting information present in its cytosolic C-terminal tail. Our data indicate that glucose metabolized in the outer segment must first enter through other parts of the photoreceptor cell. Consequently, the entire energy supply of the outer segment is dependent on diffusion of energy-rich substrates through the thin connecting cilium that links this compartment to the rest of the cell.

Mitochondria Contribute to NADPH Generation in Mouse Rod Photoreceptors

“…It had been suggested (27) that the pentose phosphate pathway in the rod outer segment could potentially supply all the NADPH reducing equivalents necessary for the reduction of all-trans-retinal to retinol. More recent studies have shown that glucose enters through transporter Glut-1 into the inner segment (28), where it is phosphorylated to glucose-6-phosphate by hexokinases I and II (29). Glucose-6-phosphate can then be utilized through the pentose phosphate pathway to generate NADPH from NADP ϩ .…”

Retinal energy demands control vascular supply of the retina in development and disease: The role of neuronal lipid and glucose metabolism

“…Metabolic pathways are labeled in purple, and the enzymes controlling critical metabolic steps are shown in blue boxes. Figure modified, with permission, from (Gospe et al, 2010; Vander Heiden et al, 2009). …”

Roles of Glucose in Photoreceptor Survival

“…Both rod-dominated (19 -21) and cone-dominated (22) retinas use glucose in this manner. Glucose enters PRs through the Glut-1 transporters located in the inner segment of PRs (23). There it is phosphorylated by hexokinase 2 (24) and then diffuses to other parts of the cell.…”