Impaired proteostasis contributes to renal tubular dysgenesis.

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...

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Autores principales:	Rita Machado de Oliveira, Zrinka Marijanovic, Filipe Carvalho, Gabriel Miltenberger Miltényi, Joana Estevão Matos, Sandra Tenreiro, Sónia Oliveira, Francisco Javier Enguita, Rosário Stone, Tiago Fleming Outeiro
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f62fe3d6a7a14559a841f167bb0155bc
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spelling	oai:doaj.org-article:f62fe3d6a7a14559a841f167bb0155bc2021-11-18T06:52:19ZImpaired proteostasis contributes to renal tubular dysgenesis.1932-620310.1371/journal.pone.0020854https://doaj.org/article/f62fe3d6a7a14559a841f167bb0155bc2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21695262/?tool=EBIhttps://doaj.org/toc/1932-6203Protein 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.Rita Machado de OliveiraZrinka MarijanovicFilipe CarvalhoGabriel Miltenberger MiltényiJoana Estevão MatosSandra TenreiroSónia OliveiraFrancisco Javier EnguitaRosário StoneTiago Fleming OuteiroPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 6, p e20854 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rita Machado de Oliveira Zrinka Marijanovic Filipe Carvalho Gabriel Miltenberger Miltényi Joana Estevão Matos Sandra Tenreiro Sónia Oliveira Francisco Javier Enguita Rosário Stone Tiago Fleming Outeiro Impaired proteostasis contributes to renal tubular dysgenesis.
description	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.
format	article
author	Rita Machado de Oliveira Zrinka Marijanovic Filipe Carvalho Gabriel Miltenberger Miltényi Joana Estevão Matos Sandra Tenreiro Sónia Oliveira Francisco Javier Enguita Rosário Stone Tiago Fleming Outeiro
author_facet	Rita Machado de Oliveira Zrinka Marijanovic Filipe Carvalho Gabriel Miltenberger Miltényi Joana Estevão Matos Sandra Tenreiro Sónia Oliveira Francisco Javier Enguita Rosário Stone Tiago Fleming Outeiro
author_sort	Rita Machado de Oliveira
title	Impaired proteostasis contributes to renal tubular dysgenesis.
title_short	Impaired proteostasis contributes to renal tubular dysgenesis.
title_full	Impaired proteostasis contributes to renal tubular dysgenesis.
title_fullStr	Impaired proteostasis contributes to renal tubular dysgenesis.
title_full_unstemmed	Impaired proteostasis contributes to renal tubular dysgenesis.
title_sort	impaired proteostasis contributes to renal tubular dysgenesis.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/f62fe3d6a7a14559a841f167bb0155bc
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_version_	1718424330105257984

Impaired proteostasis contributes to renal tubular dysgenesis.

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