Multiple functions are recognized and proposed for the plasma vitamin D binding protein (DBP, Gc, globulin). A research program is proposed to continue and develop strategies to investigate these functions. Procedures are designed to determine the various binding domains for C5a, G-actin and vitamin D sterols, as well as synthesize peptides reflecting these functions for the development of immunoprobes and cell studies designed to help understand the nature of cell-surface DBP and its possible internalization and disposition. These studies will determine whether some DBP functions are inter-related, such as C5a receptor mechanisms for targeted sterol delivery to leukocytes and/or degradation of actin scavenged by DBP binding, although a specific DBP receptor on cell surfaces will also be sought and, as indicated, characterized and sequenced. The role of DBP in chemotaxis will be explored by fully characterizing its association with C5a. To understand the functional and evolutionary differences of earlier DBP forms, cross-hybridization studies will permit the isolation of avian and pre-avian vertebrate DBP genes and cDNA's. Important functions of DBP will be analyzed in transgenic mice that over express the rat DBP gene and its protein product, thereby allowing studies of sterol availability in vitamin D deficiency and intoxication, as well as their resistance to actin toxicity. The studies proposed will lead to an improved understanding of the roles of DBP in sterol transport and delivery, actin scavenger mechanisms and regulations of chemotaxis, as well as the nature of the DBP-cell surface disposition.
| Tang, W X; Bazaraa, H M; Magiera, H et al. (1996) Electrophoretic mobility shift assay identifies vitamin D binding protein (Gc-globulin) in human, rat, and mouse sera. Anal Biochem 237:245-51 |
| Matsuoka, L Y; Wortsman, J; Haddad, J G et al. (1990) Skin types and epidermal photosynthesis of vitamin D3. J Am Acad Dermatol 23:525-6 |
| Haddad, J G; Aden, D P; Aw, T C (1989) Plasma carriers influence the uptake of cholecalciferol by human hepatoma-derived cells. J Bone Miner Res 4:243-7 |
