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Mouse transcobalamin has features resembling both human transcobalamin and haptocorrin.

Hygum K, Lildballe DL, Greibe EH, Morkbak AL, Poulsen SS, Sorensen BS, Petersen TE, Nexo E - PLoS ONE (2011)

Bottom Line: Subsequent sequencing identified the protein as TC.Analysis of the TC-mRNA level showed a high TC transcript level in these glands and also in the kidney.Our results suggest that the Cbl-binding proteins present in the circulation and exocrine glands may vary amongst species.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.

ABSTRACT
In humans, the cobalamin (Cbl) -binding protein transcobalamin (TC) transports Cbl from the intestine and into all the cells of the body, whereas the glycoprotein haptocorrin (HC), which is present in both blood and exocrine secretions, is able to bind also corrinoids other than Cbl. The aim of this study is to explore the expression of the Cbl-binding protein HC as well as TC in mice. BLAST analysis showed no homologous gene coding for HC in mice. Submaxillary glands and serum displayed one protein capable of binding Cbl. This Cbl-binding protein was purified from 300 submaxillary glands by affinity chromatography. Subsequent sequencing identified the protein as TC. Further characterization in terms of glycosylation status and binding specificity to the Cbl-analogue cobinamide revealed that mouse TC does not bind Concanavalin A sepharose (like human TC), but is capable of binding cobinamide (like human HC). Antibodies raised against mouse TC identified the protein in secretory cells of the submaxillary gland and in the ducts of the mammary gland, i.e. at locations where HC is also found in humans. Analysis of the TC-mRNA level showed a high TC transcript level in these glands and also in the kidney. By precipitation to insolubilised antibodies against mouse TC, we also showed that >97% of the Cbl-binding capacity and >98% of the Cbl were precipitated in serum. This indicates that TC is the only Cbl-binding protein in the mouse circulation. Our data show that TC but not HC is present in the mouse. Mouse TC is observed in tissues where humans express TC and/or HC. Mouse TC has features in common with both human TC and HC. Our results suggest that the Cbl-binding proteins present in the circulation and exocrine glands may vary amongst species.

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The binding affinities of mouse and human Cbl-binding proteins towards Cbl and Cbi.The binding affinities of the Cbl-binder from mouse submaxillary glands (mouse), human TC, and human HC towards (A) Cbl and (B) Cbi (see Materials and Methods for details).
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pone-0020638-g001: The binding affinities of mouse and human Cbl-binding proteins towards Cbl and Cbi.The binding affinities of the Cbl-binder from mouse submaxillary glands (mouse), human TC, and human HC towards (A) Cbl and (B) Cbi (see Materials and Methods for details).

Mentions: Mouse Cbl-binder, human HC, and human TC showed comparable binding curves for binding of Cbl, Figure 1A, supporting a comparable affinity towards Cbl for the three proteins. In contrast the binding curves for Cbi showed marked differences, Figure 1B. Kd for binding of Cbi to each of the proteins were estimated as the concentration of Cbi able to displace 50% of labeld Cbl from the binder. In accord with previous work [15] Kd for human HC (<0.5 nmol/L) was low compared to Kd for human TC ( 300 nmol/L). The mouse Cbl-binder bound Cbi better than human TC, but not as efficiently as human HC and showed a Kd of 2 nmol/L.


Mouse transcobalamin has features resembling both human transcobalamin and haptocorrin.

Hygum K, Lildballe DL, Greibe EH, Morkbak AL, Poulsen SS, Sorensen BS, Petersen TE, Nexo E - PLoS ONE (2011)

The binding affinities of mouse and human Cbl-binding proteins towards Cbl and Cbi.The binding affinities of the Cbl-binder from mouse submaxillary glands (mouse), human TC, and human HC towards (A) Cbl and (B) Cbi (see Materials and Methods for details).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3105116&req=5

pone-0020638-g001: The binding affinities of mouse and human Cbl-binding proteins towards Cbl and Cbi.The binding affinities of the Cbl-binder from mouse submaxillary glands (mouse), human TC, and human HC towards (A) Cbl and (B) Cbi (see Materials and Methods for details).
Mentions: Mouse Cbl-binder, human HC, and human TC showed comparable binding curves for binding of Cbl, Figure 1A, supporting a comparable affinity towards Cbl for the three proteins. In contrast the binding curves for Cbi showed marked differences, Figure 1B. Kd for binding of Cbi to each of the proteins were estimated as the concentration of Cbi able to displace 50% of labeld Cbl from the binder. In accord with previous work [15] Kd for human HC (<0.5 nmol/L) was low compared to Kd for human TC ( 300 nmol/L). The mouse Cbl-binder bound Cbi better than human TC, but not as efficiently as human HC and showed a Kd of 2 nmol/L.

Bottom Line: Subsequent sequencing identified the protein as TC.Analysis of the TC-mRNA level showed a high TC transcript level in these glands and also in the kidney.Our results suggest that the Cbl-binding proteins present in the circulation and exocrine glands may vary amongst species.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.

ABSTRACT
In humans, the cobalamin (Cbl) -binding protein transcobalamin (TC) transports Cbl from the intestine and into all the cells of the body, whereas the glycoprotein haptocorrin (HC), which is present in both blood and exocrine secretions, is able to bind also corrinoids other than Cbl. The aim of this study is to explore the expression of the Cbl-binding protein HC as well as TC in mice. BLAST analysis showed no homologous gene coding for HC in mice. Submaxillary glands and serum displayed one protein capable of binding Cbl. This Cbl-binding protein was purified from 300 submaxillary glands by affinity chromatography. Subsequent sequencing identified the protein as TC. Further characterization in terms of glycosylation status and binding specificity to the Cbl-analogue cobinamide revealed that mouse TC does not bind Concanavalin A sepharose (like human TC), but is capable of binding cobinamide (like human HC). Antibodies raised against mouse TC identified the protein in secretory cells of the submaxillary gland and in the ducts of the mammary gland, i.e. at locations where HC is also found in humans. Analysis of the TC-mRNA level showed a high TC transcript level in these glands and also in the kidney. By precipitation to insolubilised antibodies against mouse TC, we also showed that >97% of the Cbl-binding capacity and >98% of the Cbl were precipitated in serum. This indicates that TC is the only Cbl-binding protein in the mouse circulation. Our data show that TC but not HC is present in the mouse. Mouse TC is observed in tissues where humans express TC and/or HC. Mouse TC has features in common with both human TC and HC. Our results suggest that the Cbl-binding proteins present in the circulation and exocrine glands may vary amongst species.

Show MeSH