Cobalamin transport proteins and their cell-surface receptors.
The primary function of cobalamin (Cbl; vitamin B12) is the formation of red blood cells and the maintenance of a healthy nervous system. Before cells can utilise dietary Cbl, the vitamin must undergo cellular transport using two distinct receptor-mediated events. First, dietary Cbl bound to gastric intrinsic factor (IF) is taken up from the apical pole of ileal epithelial cells via a 460 kDa receptor, cubilin, and is transported across the cell bound to another Cbl-binding protein, transcobalamin II (TC II). Second, plasma TC II-Cbl is taken up by cells that need Cbl via the TC II receptor (TC II-R), a 62 kDa protein that is expressed as a functional dimer in cellular plasma membranes. Human Cbl deficiency can develop as a result of acquired or inherited dysfunction in either of these two transmembrane transport events. This review focuses on the biochemical, cellular and molecular aspects of IF and TC II and their cell-surface receptors.
Division of Gastroenterology and Hepatology, Department of Medicine, Medical College of Wisconsin and Clement Zablocki Veterans Medical Center, Milwaukee, WI 53295, USA. seethara@mcw.edu
Bellur
B
Seetharam
Raghunatha R
RR
Yammani
D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology; D007437:Intrinsic Factor / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014155:Transcobalamins / Q000378:metabolism*; D014805:Vitamin B 12 / Q000378:metabolism; D014806:Vitamin B 12 Deficiency / Q000235:genetics / Q000378:metabolism
D011956:Receptors, Cell Surface; D014155:Transcobalamins; C029486:intrinsic factor-cobalamin receptor; C028176:transcobalamin receptor; D007437:Intrinsic Factor; D014805:Vitamin B 12