Article ; Online: Impaired intestinal calcium absorption in protein 4.1R-deficient mice due to altered expression of plasma membrane calcium ATPase 1b (PMCA1b).
The Journal of biological chemistry
2013 Volume 288, Issue 16, Page(s) 11407–11415
Abstract: ... where it co-localizes with PMCA1b (plasma membrane calcium ATPase 1b). Expression of PMCA1b in enterocytes was ... decreased in 4.1(-/-) mice. 4.1R directly associated with PMCA1b, and the association involved the membrane ... enabled us to define a functional role for 4.1R in small intestinal calcium absorption through regulation ...
| Abstract | Protein 4.1R was first identified in the erythrocyte membrane skeleton. It is now known that the protein is expressed in a variety of epithelial cell lines and in the epithelia of many tissues, including the small intestine. However, the physiological function of 4.1R in the epithelial cells of the small intestine has not so far been explored. Here, we show that 4.1R knock-out mice exhibited a significantly impaired small intestinal calcium absorption that resulted in secondary hyperparathyroidism as evidenced by increased serum 1,25-(OH)2-vitamin D3 and parathyroid hormone levels, decreased serum calcium levels, hyperplasia of the parathyroid, and demineralization of the bones. 4.1R is located on the basolateral membrane of enterocytes, where it co-localizes with PMCA1b (plasma membrane calcium ATPase 1b). Expression of PMCA1b in enterocytes was decreased in 4.1(-/-) mice. 4.1R directly associated with PMCA1b, and the association involved the membrane-binding domain of 4.1R and the second intracellular loop and C terminus of PMCA1b. Our findings have enabled us to define a functional role for 4.1R in small intestinal calcium absorption through regulation of membrane expression of PMCA1b. |
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| MeSH term(s) | Animals ; Calcitriol/blood ; Calcitriol/genetics ; Calcium/metabolism ; Enterocytes/metabolism ; Gene Expression Regulation, Enzymologic ; Intestinal Absorption ; Mice ; Mice, Knockout ; Microfilament Proteins/genetics ; Microfilament Proteins/metabolism ; Parathyroid Hormone/blood ; Parathyroid Hormone/genetics ; Plasma Membrane Calcium-Transporting ATPases/biosynthesis ; Plasma Membrane Calcium-Transporting ATPases/genetics ; Protein Structure, Tertiary | |||||
| Chemical Substances | Epb41 protein, mouse ; Microfilament Proteins ; Parathyroid Hormone ; Pmca1b protein, mouse ; Plasma Membrane Calcium-Transporting ATPases (EC 3.6.3.8) ; Calcitriol (FXC9231JVH) ; Calcium (SY7Q814VUP) | |||||
| Language | English | |||||
| Publishing date | 2013-03-04 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 2997-x | |||||
| ISSN | 1083-351X ; 0021-9258 | |||||
| ISSN (online) | 1083-351X | |||||
| ISSN | 0021-9258 | |||||
| DOI | 10.1074/jbc.M112.436659 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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