Physiological mechanisms of nutrient transport: calciferols and vitamin D-binding protein

Biologically active metabolites of vitamin D affect cell growth and differentiation, and thereby contribute to physiological regulation. Vitamin D-binding protein (DBP) binds 25-hydroxycholecalciferol and other D metabolites, and participates in their delivery to cells. Based on evidence for receptor-mediated endocytosis (RME) of DBP, experiments were performed to analyze DBP transport in animal tissues and cells. The results provide evidence that DBP RME can occur through a pathway that differs from the well-characterized clathrin-dependent endocytic pathway of transferrin (Tf, circulatory iron carrier protein). Moreover, cell growth density has differential effects on (a) the endocytosis of Tf and DBP, and (b) epidermal growth factor-mediated stimulation of DBP endocytosis. Comparative analyses of tissues and cells provides evidence for possible hormonal (e.g., estradiol) and aging effects on transport and receptor-binding parameters of DBP and other nutrient carrier proteins.