Multiplexed 3Cs identifies novel genetic interactions in Glut1 deficiency syndrome

  • 2 Years 2020/2022
  • 49.947€ Total Award

Glucose transporter type 1 (GLUT1) is a protein that captures and promotes the uptake of energy, in the form of glucose, into the cell from its surroundings. Since glucose can’t easily cross the blood brain barrier, GLUT1 is required to supply the energy necessary for brain growth and function. The SLC2A1 gene, provides the blueprints for making the GLUT1 protein, and mutations in this gene lead to a metabolic disorder known as GLUT1 deficiency. This debilitating condition does not have a known cure and a ketogenic diet, which is high in fat and low in carbohydrates and protein is the standard treatment. This diet produces ketone bodies that bypass the GLUT1 defect and cross the blood-brain barrier to fuel the brain. The lack of alternative therapies is partially due to a poor understanding of the mechanisms that regulate GLUT1 transport from within cellular vesicles, where it resides, to the cell membrane, where it can promote glucose uptake into the cell. Proper GLUT1 transport requires a functional protein complex, known as a retromer as well as the assistance of the cellular recycling system known as autophagy. Autophagy helps sustain cellular metabolism under conditions of stress and was recently shown to promotes glucose uptake by favoring the localization of GLUT1 to the cell surface. Therefore, a more complete understanding of the role autophagy and the retromer complex play in GLUT1 transport will help identify new therapies for the treatment of GLUT1 deficiency.

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