Regulation of expression of transcobalamin II receptor in the rat.
Surface and intracellular membrane distribution and hormonal regulation of transcobalamin II receptor (TC II-R) activity and protein levels have been studied in an effort to understand its regulation of expression in the rat. TC II-R activity and the levels of the 62 kDa monomeric and 124 kDa dimeric forms of TC II-R were highest in the rat kidney and intestine, and in these tissues the receptor expression was not dependent upon the postnatal development of the rat. TC II-R expression was uniform in the various regions of the gut. Surface membrane distribution of TC II-R in the kidney revealed the expression of the 124 kDa dimer form of TC II-R in the apical and basolateral membranes in the ratio of 1:10. Further subcellular distribution of TC II-R in the kidney revealed the expression of the 124 kDa dimer in the intermicrovillar clefts and clathrin-coated vesicles and the 62 kDa monomer in the microsomes. Neither the monomer nor the dimer could be detected in the early endosomes or lysosomes. Membrane TC II-R activity and TC II-R protein levels and cobalamin (Cbl; vitamin B12) transport in vivo were inhibited by about 90% in adrenalectomized rats and all three returned to normal levels by oral treatment of these animals with cortisone acetate. In contrast, thyroidectomy or experimentally induced diabetes had no effect on TC II-R activity or Cbl transport. Based on these observations, we suggest that TC II-R expression is not developmentally or regionally regulated in rat renal and intestinal membranes and its expression in the kidney is asymmetrically distributed between the apical (10%) and basolateral (90%) membranes. In addition, our results also show that the dimerization of TC II-R is a post-microsomal event and that the expression of TC II-R and plasma Cbl transport is regulated by cortisone.
Bose
S
S
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226, USA.
Seetharam
S
S
Hammond
T G
TG
Seetharam
B
B
D000315:Adrenalectomy; D000375:Aging / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000254:growth & development / Q000378:metabolism*; D007422:Intestines / Q000254:growth & development; D007668:Kidney / Q000254:growth & development / Q000378:metabolism; D046911:Macromolecular Substances; D008297:Male; D008970:Molecular Weight; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000378:metabolism; D012016:Reference Values; D013965:Thyroidectomy; D013974:Thyroxine / Q000494:pharmacology; D014155:Transcobalamins / Q000378:metabolism
D007328:Insulin; D046911:Macromolecular Substances; D011956:Receptors, Cell Surface; D014155:Transcobalamins; C028176:transcobalamin receptor; D013974:Thyroxine