Transcobalamin II — Cobalamin binding sites are present on rabbit germ cells

Boukhzer, El Bachir; Ennya, A.; Felden, F.; Gérard, A.; Nexø, Ebba; Nicolas, Jean‐Pierre; Gérard, Hubert; Guéant, Jean‐Louis

doi:10.1016/0167-4889(92)90019-8

Cited by 9 publications

(2 citation statements)

References 21 publications

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“…Binding sites for TC-B12 have previously been described (10,11,(34)(35)(36)(37)(38)(39) on several different cell types including fibroblasts, hepatocytes, renal tubule cells, and syncytiotrophoblasts. The Ca2+-sensitive binding sites previously described (10,11) on renal proximal tubule cells may be identical to megalin, whereas TC-B12 binding sites on several nonepithelial cell types not expressing megalin must be of different origin.…”

Section: Discussionmentioning

confidence: 99%

Megalin-mediated endocytosis of transcobalamin-vitamin-B12 complexes suggests a role of the receptor in vitamin-B12 homeostasis.

Moestrup

Birn

Fischer

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

199

135

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Kidney cortex is a main target for circulating vitamin B12 (cobalamin) in complex with transcobalamin (TC). Ligand blotting of rabbit kidney cortex with rabbit 1251-TC-B12 and human TC-57Co-B12 revealed an exclusive binding to megalin, a 600-kDa endocytic receptor present in renal proximal tubule epithelium and other absorptive epithelia. The Vitamin B12 and other cobalamins (B12)ti form complexes with three mammalian tissue fluid proteins. These include gastric intrinsic factor, transcobalamin (TC) present in plasma, and haptocorrin found in most secretions. Intrinsic factor secreted from the stomach is essential for the intestinal uptake of vitamin B12, whereas TC facilitates the cellular uptake of B12 from plasma and various tissue fluids into a wide spectrum of cells (1, 2). Lack of synthesis of either intrinsic factor (3) or TC (4) leads to hematological, gastrointestinal, and/or neurological disorders.B12 is widely distributed in the mammalian organism and high concentrations are seen in the liver and kidney. Animal studies (5-7) have shown that the kidney plays a major role in the regulation of the plasma B12 level by maintaining a pool of free B12. On the other hand, liver B12 is largely bound to the Bi2-dependent enzymes, methylmalonyl coenzyme A mutase and methionine synthetase. During deficiency, B12 is released from the kidney rather than from the enzyme-bound pool of the vitamin in the liver and other organs (7). Radiolabeled B12 taken up in the kidney is localized exclusively in the renal proximal tubules (8). B12 is only taken up in the kidney when it is bound to TC, and if administrated B12 exceeds the saturation level of plasma TC, free B12 is excreted in the urine (9). In agreement with this fact, high-affinity binding sites for complexes, but not for free B12, have been shown on the luminal surface of isolated rat (10) and hog tubule cells (11). Interestingly, the proportional uptake in the kidney of dietary B12 or intravenously administrated TC-B12 is higher at a high B12 load in the organism, and a regulatory mechanism for uptake and storage of B12 in the kidney has been suggested (5,6,8,10,12).Megalin [previously designated glycoprotein 330 (gp330) or Heymann Nephritis autoantigen] is a 600-kDa endocytosismediating membrane protein expressed in the tubule epithelium (13-15) and some other absorptive epithelia, e.g., in yolk sac, lung, retina, and inner ear (16,17). Megalin belongs to the low density lipoprotein receptor gene family (18) and has been shown to bind different substances including clusterin (19), polybasic aminoglycoside drugs (20), and several of the proteins binding to the homologous 600-kDa a2-macroglobulin receptor/low density lipoprotein receptor-related protein (a2MR/LRP)-e.g., the 39-44 kDa receptor-associated protein (RAP) and plasminogen activators (free or in complex with type-1 inhibitor) (for reviews, see refs. 21 and 22

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Section: Discussionmentioning

confidence: 99%

Megalin-mediated endocytosis of transcobalamin-vitamin-B12 complexes suggests a role of the receptor in vitamin-B12 homeostasis.

Moestrup

Birn

Fischer

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

199

135

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“…C'est ainsi que le fer, associ~ ~ sa prot~ine de liaison, la transferrine, est transportS, via le cytoplasme Sertolien, jusqu'au compartiment des cellules germinales [26,28,34]. L'existence d'un m~canisme similaire est sugg~r~ pour le transfert du cuivre grace son transport par la c~ruloplasmine [26] et pour la vitamine B12 li~e ~ la transcobalamine [2].…”

Section: Introductionunclassified

Germinal cell lineage possess the capacity of sex steroid-binding protein (hSBP) internalization: Transmission electron microscopy (TEM) autohistoradiographic study

Bedjou¹,

Gérard

Felden

et al. 1995

Androl.

Self Cite

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RESUMEI1 a dt~ rdcemment ddmontrd que les cellules spermatogdndtiques de rat sont capables de lier et d'internaliser spdcifiquement l'androgen-binding protein de rat (ABPr). De m~me les cellules spermatog~ndtiques du macaque, sont capables de lier et d'internaliser spdcifiquement la sex steroid-binding protein humaine (SBPh).Cette dtude consiste ~ tester si des interactions entre les cellules spermatogdndtiques et les prot~ines de liaison des st~roides existent dgalement chez l'homme. Les cellules germinales proviennent d'une part des biopsies testiculaires de patients hypofertiles et d'autre part de pulpectomies indiqu~es pour cancer prostatique.Les observations en MET rdv~lent la prdsence de deux types de structures relids ~ l'endocytose dans les cellules spermatogdndtiques. Premi~rement, les puits et vdsicules recouverts de 96 _+ 10 nm de diam~tre, associds ~ la membrane plasmique. Deuxi~mement, les endosomes prdcoces (vdsicules non recouvertes) de 225 -+ 60 nm de diam~tre localisds ~ la pdriph~rie du cytoplasme ainsi que les endosomes tardifs, souvent organisds en corps multiv~siculaires (CMV) dans le cytoplasme pdrinucldaire. Ces deux types de structures de l'appareil endocytaire sont prdsents ~ tous les stades de maturation des cellules germinales. Les vdsicules non recouvertes sont toujours plus nombreuses que les vdsicules recouvertes quel que soit le stade.Les cellules germinales isoldes et in situ maintenues dans l'dpithdlium sdminif/~re ont ~td exposdes au milieu de culture contenant le complexe SBPh purifi~e (~ partir de sdrum de femme enceinte) -A6-testotdrone tritide (80 000 cpm/ml, 30 ng) photomarqude. L'~tude des interactions SBPh/ cellules germinales est fond~e sur les 528 analyses qualitatives et quantitatives du marquage r~v~l~ par autohistoradiographie en MET.

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Cellular Surface Receptors Important for Vitamin B₁₂Nutrition

Moestrup

1998

Vitamin B12 and B12‐Proteins

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Transcobalamin II — Cobalamin binding sites are present on rabbit germ cells

Cited by 9 publications

References 21 publications

Megalin-mediated endocytosis of transcobalamin-vitamin-B12 complexes suggests a role of the receptor in vitamin-B12 homeostasis.

Megalin-mediated endocytosis of transcobalamin-vitamin-B12 complexes suggests a role of the receptor in vitamin-B12 homeostasis.

Germinal cell lineage possess the capacity of sex steroid-binding protein (hSBP) internalization: Transmission electron microscopy (TEM) autohistoradiographic study

Cellular Surface Receptors Important for Vitamin B₁₂Nutrition

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Transcobalamin II — Cobalamin binding sites are present on rabbit germ cells

Cited by 9 publications

References 21 publications

Megalin-mediated endocytosis of transcobalamin-vitamin-B12 complexes suggests a role of the receptor in vitamin-B12 homeostasis.

Megalin-mediated endocytosis of transcobalamin-vitamin-B12 complexes suggests a role of the receptor in vitamin-B12 homeostasis.

Germinal cell lineage possess the capacity of sex steroid-binding protein (hSBP) internalization: Transmission electron microscopy (TEM) autohistoradiographic study

Cellular Surface Receptors Important for Vitamin B12Nutrition

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Cellular Surface Receptors Important for Vitamin B₁₂Nutrition