Vitamin D–binding protein

Vitamin D–binding protein is a member of the albumin family, and its gene is found in all vertebrate taxa. DBP has a single binding cleft at the surface of its domain I and is responsible for the transport of all vitamin D metabolites, notably 25-hydroxyvitamin D (25(OH)D). Only a small fraction of 25(OH)D circulates in serum as “free” 25(OH)D, while some 25(OH)D is considered “bioavailable” by binding to albumin. Only free and bioavailable fractions have easy access to intracellular compartments. Renal proximal tubular cells express megalin, allowing the endocytic reuptake of DBP and its ligands, thereby preventing urinary loss of vitamin D. Similar uptake of DBP and its vitamin D cargo may also take place in several extra-renal tissues that express megalin. DBP-null mice have very low serum levels of vitamin D metabolites but no vitamin D–related disease. A similar phenotype has also been observed for two humans reported to have mutations in the gene for DBP (Group Specific Protein, GC). DBP also binds to monomeric actin, thereby preventing the formation of fibrillar actin and obstruction of the microcirculation after extensive tissue damage. Recently, a role for DBP as an intracellular binder of actin has been described.