title: Impaired intestinal calcium absorption in protein 4.1R-deficient mice due to altered expression of plasma membrane calcium ATPase 1b (PMCA1b).
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.
authors: Red Cell Physiology Laboratory, New York Blood Center, New York, New York 10065, USA.
authors: Congrong
authors: C
authors: Liu
authors: Haibao
authors: H
authors: Weng
authors: Lixiang
authors: L
authors: Chen
authors: Shaomin
authors: S
authors: Yang
authors: Hua
authors: H
authors: Wang
authors: Gargi
authors: G
authors: Debnath
authors: Xinhua
authors: X
authors: Guo
authors: Liancheng
authors: L
authors: Wu
authors: Narla
authors: N
authors: Mohandas
authors: Xiuli
authors: X
authors: An
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000097:blood / Q000235:genetics; D002118:Calcium / Q000378:metabolism*; D020895:Enterocytes / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D007408:Intestinal Absorption; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000097:blood / Q000235:genetics; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000096:biosynthesis* / Q000235:genetics; D017434:Protein Structure, Tertiary
chemical_list: C514956:Epb41 protein, mouse; D008840:Microfilament Proteins; D010281:Parathyroid Hormone; C556012:Pmca1b protein, mouse; D053499:Plasma Membrane Calcium-Transporting ATPases; D002117:Calcitriol; D002118:Calcium