Rod-derived cone viability factor–Basigin-1 protein-protein interface (RdCVF–BSG1)

The Rod-derived cone viability factor (RdCVF) and Basigin-1 (BSG1) protein-protein interface is a critical metabolic signaling pathway in the retina responsible for the survival of cone photoreceptors (Ait-Ali et al., 2015, Cell). RdCVF is a truncated thioredoxin-like protein encoded by the NXNL1 gene and secreted by rod photoreceptors; it binds specifically to the BSG1 receptor, a retina-specific splice variant of Basigin (CD147), located on the surface of cones (Lambard et al., 2010, Journal of Alzheimer's Disease). This interaction facilitates the recruitment of the glucose transporter GLUT1 (SLC2A1) to the cone cell membrane, thereby stimulating glucose uptake and aerobic glycolysis, which are essential for the structural integrity and function of cones (Ait-Ali et al., 2015, Cell). In diseases like Retinitis Pigmentosa, the primary loss of rods leads to a depletion of RdCVF, resulting in secondary cone starvation and eventual blindness (Leveillard et al., 2004, Nature Genetics). Therapeutic strategies targeting this interface, such as the gene therapy SPVN06, aim to preserve cone-mediated vision by restoring RdCVF levels regardless of the underlying genetic mutation causing rod death (SparingVision, 2024). This approach represents a mutation-agnostic method for treating inherited retinal degenerations by addressing the metabolic deficit that leads to cone loss.

Other names

NXNL1-BSG1 interactionRod-derived cone viability factor receptor complexRdCVF-BSG1 complexNucleoredoxin-like 1-Basigin interaction

Binding of RdCVF to the Basigin-1 receptor on cone photoreceptors triggers the recruitment of the glucose transporter GLUT1 (SLC2A1) to the cell surface, increasing glucose uptake and aerobic glycolysis to maintain cone viability (Ait-Ali et al., 2015, Cell).