Unique Regulation of Na-K-ATPase during Growth and Maturation of Intestinal Epithelial Cells
Na-K-ATPase on the basolateral membrane provides the favorable transcellular Na gradient for the proper functioning of Na-dependent nutrient co-transporters on the brush border membrane (BBM) of enterocytes. As cells mature from crypts to villus, Na-K-ATPase activity doubles, to accommodate for the...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-06-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/8/6/593 |
| _version_ | 1827884187538948096 |
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| author | Niraj Nepal Subha Arthur Uma Sundaram |
| author_facet | Niraj Nepal Subha Arthur Uma Sundaram |
| author_sort | Niraj Nepal |
| collection | DOAJ |
| description | Na-K-ATPase on the basolateral membrane provides the favorable transcellular Na gradient for the proper functioning of Na-dependent nutrient co-transporters on the brush border membrane (BBM) of enterocytes. As cells mature from crypts to villus, Na-K-ATPase activity doubles, to accommodate for the increased BBM Na-dependent nutrient absorption. However, the mechanism of increased Na-K-ATPase activity during the maturation of enterocytes is not known. Therefore, this study aimed to determine the mechanisms involved in the functional transition of Na-K-ATPase during the maturation of crypts to villus cells. Na-K-ATPase activity gradually increased as IEC-18 cells matured in vitro from day 0 (crypts) through day 4 (villus) of post-confluence. mRNA abundance and Western blot studies showed no change in the levels of Na-K-ATPase subunits α1 and β1 from 0 to 4 days post-confluent cells. However, Na-K-ATPase α1 phosphorylation levels on serine and tyrosine, but not threonine, residues gradually increased. These data indicate that as enterocytes mature from crypt-like to villus-like in culture, the functional activity of Na-K-ATPase increases secondary to altered affinity of the α1 subunit to extracellular K<sup>+</sup>, in order to accommodate the functional preference of the intestinal cell type. This altered affinity is likely due to increased phosphorylation of the α1 subunit, specifically at serine and tyrosine residues. |
| first_indexed | 2024-03-12T19:25:48Z |
| format | Article |
| id | doaj.art-86ecbf68a108470d8dc6fa06c0309363 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T19:25:48Z |
| publishDate | 2019-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-86ecbf68a108470d8dc6fa06c03093632023-08-02T04:53:36ZengMDPI AGCells2073-44092019-06-018659310.3390/cells8060593cells8060593Unique Regulation of Na-K-ATPase during Growth and Maturation of Intestinal Epithelial CellsNiraj Nepal0Subha Arthur1Uma Sundaram2Department of Clinical and Translational Sciences and Appalachian Clinical and Translational Science Institute, Joan C. Edwards School of Medicine, Marshall University, 1600 Medical Center Drive, Huntington, WV 25701, USADepartment of Clinical and Translational Sciences and Appalachian Clinical and Translational Science Institute, Joan C. Edwards School of Medicine, Marshall University, 1600 Medical Center Drive, Huntington, WV 25701, USADepartment of Clinical and Translational Sciences and Appalachian Clinical and Translational Science Institute, Joan C. Edwards School of Medicine, Marshall University, 1600 Medical Center Drive, Huntington, WV 25701, USANa-K-ATPase on the basolateral membrane provides the favorable transcellular Na gradient for the proper functioning of Na-dependent nutrient co-transporters on the brush border membrane (BBM) of enterocytes. As cells mature from crypts to villus, Na-K-ATPase activity doubles, to accommodate for the increased BBM Na-dependent nutrient absorption. However, the mechanism of increased Na-K-ATPase activity during the maturation of enterocytes is not known. Therefore, this study aimed to determine the mechanisms involved in the functional transition of Na-K-ATPase during the maturation of crypts to villus cells. Na-K-ATPase activity gradually increased as IEC-18 cells matured in vitro from day 0 (crypts) through day 4 (villus) of post-confluence. mRNA abundance and Western blot studies showed no change in the levels of Na-K-ATPase subunits α1 and β1 from 0 to 4 days post-confluent cells. However, Na-K-ATPase α1 phosphorylation levels on serine and tyrosine, but not threonine, residues gradually increased. These data indicate that as enterocytes mature from crypt-like to villus-like in culture, the functional activity of Na-K-ATPase increases secondary to altered affinity of the α1 subunit to extracellular K<sup>+</sup>, in order to accommodate the functional preference of the intestinal cell type. This altered affinity is likely due to increased phosphorylation of the α1 subunit, specifically at serine and tyrosine residues.https://www.mdpi.com/2073-4409/8/6/593Na/K-ATPaseintestinal absorptionNa-dependent nutrient co-transportcrypt cellsvillus cellscell maturation |
| spellingShingle | Niraj Nepal Subha Arthur Uma Sundaram Unique Regulation of Na-K-ATPase during Growth and Maturation of Intestinal Epithelial Cells Cells Na/K-ATPase intestinal absorption Na-dependent nutrient co-transport crypt cells villus cells cell maturation |
| title | Unique Regulation of Na-K-ATPase during Growth and Maturation of Intestinal Epithelial Cells |
| title_full | Unique Regulation of Na-K-ATPase during Growth and Maturation of Intestinal Epithelial Cells |
| title_fullStr | Unique Regulation of Na-K-ATPase during Growth and Maturation of Intestinal Epithelial Cells |
| title_full_unstemmed | Unique Regulation of Na-K-ATPase during Growth and Maturation of Intestinal Epithelial Cells |
| title_short | Unique Regulation of Na-K-ATPase during Growth and Maturation of Intestinal Epithelial Cells |
| title_sort | unique regulation of na k atpase during growth and maturation of intestinal epithelial cells |
| topic | Na/K-ATPase intestinal absorption Na-dependent nutrient co-transport crypt cells villus cells cell maturation |
| url | https://www.mdpi.com/2073-4409/8/6/593 |
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