AQP2: Mutations Associated with Congenital Nephrogenic Diabetes Insipidus and Regulation by Post-Translational Modifications and Protein-Protein Interactions
As a rare hereditary disease, congenital nephrogenic diabetes insipidus (NDI) is clinically characterized by polyuria with hyposthenuria and polydipsia. NDI results from collecting duct principal cell hyporesponsiveness or insensitivity to the antidiuretic action of arginine vasopressin (AVP). The p...
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MDPI AG
2020-09-01
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| Online Access: | https://www.mdpi.com/2073-4409/9/10/2172 |
| _version_ | 1827705393908809728 |
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| author | Chao Gao Paul J. Higgins Wenzheng Zhang |
| author_facet | Chao Gao Paul J. Higgins Wenzheng Zhang |
| author_sort | Chao Gao |
| collection | DOAJ |
| description | As a rare hereditary disease, congenital nephrogenic diabetes insipidus (NDI) is clinically characterized by polyuria with hyposthenuria and polydipsia. NDI results from collecting duct principal cell hyporesponsiveness or insensitivity to the antidiuretic action of arginine vasopressin (AVP). The principal cell-specific water channel aquaporin-2 (AQP2) plays an essential role in water reabsorption along osmotic gradients. The capacity to accumulate AQP2 in the apical plasma membrane in response to decreased fluid volume or increased plasma osmolality is critically regulated by the antidiuretic hormone AVP and its receptor 2 (AVPR2). Mutations in <i>AVPR2</i> result in X-linked recessive NDI, the most common form of inherited NDI. Genetic defects in <i>AQP2</i> cause autosomal recessive or dominant NDI. In this review, we provide an updated overview of the genetic and molecular mechanisms of congenital NDI, with a focus on the potential disease-causing mutations in <i>AVPR2</i> and <i>AQP2</i>, the molecular defects in the AVPR2 and AQP2 mutants, post-translational modifications (i.e., phosphorylation, ubiquitination, and glycosylation) and various protein-protein interactions that regulate phosphorylation, ubiquitination, tetramerization, trafficking, stability, and degradation of AQP2. |
| first_indexed | 2024-03-10T16:01:32Z |
| format | Article |
| id | doaj.art-2fcbe8c18b9147b4b370de28254d0c33 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T16:01:32Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-2fcbe8c18b9147b4b370de28254d0c332023-11-20T15:11:47ZengMDPI AGCells2073-44092020-09-01910217210.3390/cells9102172AQP2: Mutations Associated with Congenital Nephrogenic Diabetes Insipidus and Regulation by Post-Translational Modifications and Protein-Protein InteractionsChao Gao0Paul J. Higgins1Wenzheng Zhang2Department of Regenerative & Cancer Cell Biology, Albany Medical College, Albany, NY 12208, USADepartment of Regenerative & Cancer Cell Biology, Albany Medical College, Albany, NY 12208, USADepartment of Regenerative & Cancer Cell Biology, Albany Medical College, Albany, NY 12208, USAAs a rare hereditary disease, congenital nephrogenic diabetes insipidus (NDI) is clinically characterized by polyuria with hyposthenuria and polydipsia. NDI results from collecting duct principal cell hyporesponsiveness or insensitivity to the antidiuretic action of arginine vasopressin (AVP). The principal cell-specific water channel aquaporin-2 (AQP2) plays an essential role in water reabsorption along osmotic gradients. The capacity to accumulate AQP2 in the apical plasma membrane in response to decreased fluid volume or increased plasma osmolality is critically regulated by the antidiuretic hormone AVP and its receptor 2 (AVPR2). Mutations in <i>AVPR2</i> result in X-linked recessive NDI, the most common form of inherited NDI. Genetic defects in <i>AQP2</i> cause autosomal recessive or dominant NDI. In this review, we provide an updated overview of the genetic and molecular mechanisms of congenital NDI, with a focus on the potential disease-causing mutations in <i>AVPR2</i> and <i>AQP2</i>, the molecular defects in the AVPR2 and AQP2 mutants, post-translational modifications (i.e., phosphorylation, ubiquitination, and glycosylation) and various protein-protein interactions that regulate phosphorylation, ubiquitination, tetramerization, trafficking, stability, and degradation of AQP2.https://www.mdpi.com/2073-4409/9/10/2172nephrogenic diabetes insipidusAVPR2AQP2mutationtraffickingphosphorylation |
| spellingShingle | Chao Gao Paul J. Higgins Wenzheng Zhang AQP2: Mutations Associated with Congenital Nephrogenic Diabetes Insipidus and Regulation by Post-Translational Modifications and Protein-Protein Interactions Cells nephrogenic diabetes insipidus AVPR2 AQP2 mutation trafficking phosphorylation |
| title | AQP2: Mutations Associated with Congenital Nephrogenic Diabetes Insipidus and Regulation by Post-Translational Modifications and Protein-Protein Interactions |
| title_full | AQP2: Mutations Associated with Congenital Nephrogenic Diabetes Insipidus and Regulation by Post-Translational Modifications and Protein-Protein Interactions |
| title_fullStr | AQP2: Mutations Associated with Congenital Nephrogenic Diabetes Insipidus and Regulation by Post-Translational Modifications and Protein-Protein Interactions |
| title_full_unstemmed | AQP2: Mutations Associated with Congenital Nephrogenic Diabetes Insipidus and Regulation by Post-Translational Modifications and Protein-Protein Interactions |
| title_short | AQP2: Mutations Associated with Congenital Nephrogenic Diabetes Insipidus and Regulation by Post-Translational Modifications and Protein-Protein Interactions |
| title_sort | aqp2 mutations associated with congenital nephrogenic diabetes insipidus and regulation by post translational modifications and protein protein interactions |
| topic | nephrogenic diabetes insipidus AVPR2 AQP2 mutation trafficking phosphorylation |
| url | https://www.mdpi.com/2073-4409/9/10/2172 |
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