THE TRANSCOBALAMIN RECEPTOR (CD320): A VITAMIN B12 TRANSPORTER CRUCIAL FOR BRAIN ENERGY AND METABOLISM

Vitamin B12 (cobalamin) is one of thirteen essential vitamins and is critical for healthy neurological function. Severe vitamin B12 deficiency can present with balance, speech, and memory impairments, psychotic episodes, and dementia-like symptoms. Vitamin B12 is a crucial cofactor for brain energy single-carbon metabolism, necessary to produce methionine, Succinyl-CoA, and S-adenosylmethionine. Deficiency of vitamin B12, and subsequent deficiencies in methionine, Succinyl-CoA, and S-adenosylmethionine, are likely to disrupt brain energy metabolism via protein synthesis impairment, mitochondrial stress, and decreased ATP production.
The transcobalamin receptor (CD320) is chiefly responsible for transporting bioactive vitamin B12 from the blood into the CNS via endothelial cells of the blood-brain barrier. Our research group has published a translational study identifying a novel CD320 autoantibody in serum and CSF of patients who exhibited vitamin B12 deficiency exclusively in the CNS, leading to ataxia and white matter lesions (Pluvinage et al., 2024).
While the neurological importance of vitamin B12 is well established, the expression of CD320 has not been described in the nervous system. Here, we report the first characterization of CD320 expression in the mouse central and peripheral nervous systems. Immunohistochemistry of mouse tissue revealed robust CD320 expression on neurons and glia throughout the brain, spinal cord, and peripheral ganglia. The widespread CD320 expression across the nervous system suggests significant metabolic distress due to CD320 loss of function, likely also experienced in CD320 autoimmunity. Further research is needed to explore the impact of CD320 on brain health, energy, and metabolism in healthy, diseased, and aging contexts.