Unknown

Dataset Information

0

Impaired proteostasis contributes to renal tubular dysgenesis.

ABSTRACT: Protein conformational disorders are associated with the appearance, persistence, accumulation, and misprocessing of aberrant proteins in the cell. The etiology of renal tubular dysgenesis (RTD) is linked to mutations in the angiotensin-converting enzyme (ACE). Here, we report the identification of a novel ACE mutation (Q1069R) in an RTD patient. ACE Q1069R is found sequestered in the endoplasmic reticulum and is also subject to increased proteasomal degradation, preventing its transport to the cell surface and extracellular fluids. Modulation of cellular proteostasis by temperature shift causes an extension in the processing time and trafficking of ACE Q1069R resulting in partial rescue of the protein processing defect and an increase in plasma membrane levels. In addition, we found that temperature shifting causes the ACE Q1069R protein to be secreted in an active state, suggesting that the mutation does not affect the enzyme's catalytic properties.

SUBMITTER: de Oliveira RM 

PROVIDER: S-EPMC3111453 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Protein conformational disorders are associated with the appearance, persistence, accumulation, and misprocessing of aberrant proteins in the cell. The etiology of renal tubular dysgenesis (RTD) is linked to mutations in the angiotensin-converting enzyme (ACE). Here, we report the identification of a novel ACE mutation (Q1069R) in an RTD patient. ACE Q1069R is found sequestered in the endoplasmic reticulum and is also subject to increased proteasomal degradation, preventing its transport to the  ...[more]

Similar Datasets

Unknown Late Preterm Infant With Postnatal Diagnosis of Renal Tubular Dysgenesis.
| S-EPMC9290087 | biostudies-literature
Unknown Autosomal Recessive Renal Tubular Dysgenesis Caused by a Founder Mutation of Angiotensinogen.
| S-EPMC7609895 | biostudies-literature
Unknown Rapid Trio Exome Sequencing for Autosomal Recessive Renal Tubular Dysgenesis in Recurrent Oligohydramnios.
| S-EPMC8255961 | biostudies-literature
Unknown Effect of Hydrocortisone on Angiotensinogen (AGT) Mutation-Causing Autosomal Recessive Renal Tubular Dysgenesis.
| S-EPMC8065467 | biostudies-literature
Unknown Impaired Na<sup>+</sup>-K<sup>+</sup>-ATPase signaling in renal proximal tubule contributes to hyperuricemia-induced renal tubular injury.
| S-EPMC5898891 | biostudies-literature
Unknown A Premature Baby with Severe Oligohydramnios and Hypotension: a Case Report of Renal Tubular Dysgenesis.
| S-EPMC7431287 | biostudies-literature
Unknown RAAS-deficient organoids indicate delayed angiogenesis as a possible cause for autosomal recessive renal tubular dysgenesis.
| S-EPMC10710424 | biostudies-literature
Unknown Prenatal Diagnosis of Autosomal Recessive Renal Tubular Dysgenesis with Anhydramnios Caused by a Mutation in the AGT Gene.
| S-EPMC6963964 | biostudies-literature
Unknown Expanding the clinical spectrum of autosomal-recessive renal tubular dysgenesis: Two siblings with neonatal survival and review of the literature.
| S-EPMC9034669 | biostudies-literature
Unknown REST contributes to AKI-to-CKD transition through inducing ferroptosis in renal tubular epithelial cells.
| S-EPMC10393228 | biostudies-literature