scholarly journals A Novel Mutation of the Arginine Vasopressin Receptor 2 Gene in a Patient with Congenital Nephrogenic Diabetes Insipidus

2005 ◽  
Vol 14 (1) ◽  
pp. 27-33 ◽  
Author(s):  
Asako Tajima ◽  
Ichiro Miyata ◽  
Akira Katayama ◽  
Shigeru Toyoda ◽  
Yoshikatsu Eto
Keyword(s):  
Diabetes Insipidus ◽  
Arginine Vasopressin ◽  
Nephrogenic Diabetes Insipidus ◽  
Novel Mutation ◽  
Vasopressin Receptor ◽  
Congenital Nephrogenic Diabetes Insipidus

scholarly journals Valine-279 Deletion–Mutation on Arginine Vasopressin Receptor 2 Causes Obstruction in G-Protein Binding Site: A Clinical Nephrogenic Diabetes Insipidus Case and Its Sub-Molecular Pathogenic Analysis

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 301
Author(s):  
Ming-Chun Chen ◽  
Yu-Chao Hsiao ◽  
Chun-Chun Chang ◽  
Sheng-Feng Pan ◽  
Chih-Wen Peng ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Protein Binding ◽  
Diabetes Insipidus ◽  
Binding Site ◽  
G Protein ◽  
Arginine Vasopressin ◽  
Nephrogenic Diabetes Insipidus ◽  
Md Simulations ◽  
Protein Binding Site ◽  
Vasopressin Receptor

Congenital nephrogenic diabetes insipidus (CNDI) is a genetic disorder caused by mutations in arginine vasopressin receptor 2 (AVPR2) or aquaporin 2 genes, rendering collecting duct cells insensitive to the peptide hormone arginine vasopressin stimulation for water reabsorption. This study reports a first identified AVPR2 mutation in Taiwan and demonstrates our effort to understand the pathogenesis caused by applying computational structural analysis tools. The CNDI condition of an 8-month-old male patient was confirmed according to symptoms, family history, and DNA sequence analysis. The patient was identified to have a valine 279 deletion–mutation in the AVPR2 gene. Cellular experiments using mutant protein transfected cells revealed that mutated AVPR2 is expressed successfully in cells and localized on cell surfaces. We further analyzed the pathogenesis of the mutation at sub-molecular levels via long-term molecular dynamics (MD) simulations and structural analysis. The MD simulations showed while the structure of the extracellular ligand-binding domain remains unchanged, the mutation alters the direction of dynamic motion of AVPR2 transmembrane helix 6 toward the center of the G-protein binding site, obstructing the binding of G-protein, thus likely disabling downstream signaling. This study demonstrated that the computational approaches can be powerful tools for obtaining valuable information on the pathogenesis induced by mutations in G-protein-coupled receptors. These methods can also be helpful in providing clues on potential therapeutic strategies for CNDI.

scholarly journals Functional characterization of a loss-of-function mutant I324M of arginine vasopressin receptor 2 in X-linked nephrogenic diabetes insipidus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lixia Wang ◽  
Weihong Guo ◽  
Chunyun Fang ◽  
Wenli Feng ◽  
Yumeng Huang ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Arginine Vasopressin ◽  
Nephrogenic Diabetes Insipidus ◽  
Functional Characterization ◽  
Gene Mutations ◽  
Biochemical Properties ◽  
Vasopressin Receptor ◽  
Inherited Disease ◽  
Loss Of Function ◽  
Gene Encoding

AbstractX-linked nephrogenic diabetes insipidus (X-linked NDI) is a rare inherited disease mainly caused by lost-of-function mutations in human AVPR2 gene encoding arginine vasopressin receptor 2 (V2R). Our focus of the current study is on exploration of the functional and biochemical properties of Ile324Met (I324M) mutation identified in a pedigree showing as typical recessive X-linked NDI. We demonstrated that I324M mutation interfered with the conformation of complex glycosylation of V2R. Moreover, almost all of the I324M-V2R failed to express on the cell surface due to being captured by the endoplasmic reticulum control system. We further examined the signaling activity of DDAVP-medicated cAMP and ERK1/2 pathways and the results revealed that the mutant receptor lost the ability in response to DDAVP stimulation contributed to the failure of accumulation of cAMP and phosphorylated ERK1/2. Based on the characteristics of molecular defects of I324M mutant, we selected two reagents (SR49059 and alvespimycin) to determine whether the functions of I324M-V2R can be restored and we found that both compounds can significantly “rescue” I324M mutation. Our findings may provide further insights for understanding the pathogenic mechanism of AVPR2 gene mutations and may offer some implications on development of promising treatments for patients with X-linked NDI.

Hemodynamic and Coagulation Responses to 1-Desamino[8-D-Arginine] Vasopressin in Patients with Congenital Nephrogenic Diabetes Insipidus

1988 ◽  
Vol 318 (14) ◽  
pp. 881-887 ◽  
Author(s):  
Daniel G. Bichet ◽  
Mohammad Razi ◽  
Michèle Lonergan ◽  
Marie-Françoise Arthus ◽  
Vassiliki Papukna ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Arginine Vasopressin ◽  
Nephrogenic Diabetes Insipidus ◽  
Congenital Nephrogenic Diabetes Insipidus
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