Na+/H+ exchangers induce autophagy in neurons and inhibit polyglutamine-induced aggregate formation.

In polyglutamine diseases, an abnormally elongated polyglutamine results in protein misfolding and accumulation of intracellular aggregates. Autophagy is a major cellular degradative pathway responsible for eliminating unnecessary proteins, including polyglutamine aggregates. Basal autophagy constit...

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Autores principales:	Kazuya Togashi, Shuji Wakatsuki, Akiko Furuno, Shinji Tokunaga, Yoshitaka Nagai, Toshiyuki Araki
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/927628d3b37e4d47b4b246f92f5401d8
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spelling	oai:doaj.org-article:927628d3b37e4d47b4b246f92f5401d82021-11-18T08:45:09ZNa+/H+ exchangers induce autophagy in neurons and inhibit polyglutamine-induced aggregate formation.1932-620310.1371/journal.pone.0081313https://doaj.org/article/927628d3b37e4d47b4b246f92f5401d82013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24278418/?tool=EBIhttps://doaj.org/toc/1932-6203In polyglutamine diseases, an abnormally elongated polyglutamine results in protein misfolding and accumulation of intracellular aggregates. Autophagy is a major cellular degradative pathway responsible for eliminating unnecessary proteins, including polyglutamine aggregates. Basal autophagy constitutively occurs at low levels in cells for the performance of homeostatic function, but the regulatory mechanism for basal autophagy remains elusive. Here we show that the Na(+)/H(+) exchanger (NHE) family of ion transporters affect autophagy in a neuron-like cell line (Neuro-2a cells). We showed that expression of NHE1 and NHE5 is correlated to polyglutamine accumulation levels in a cellular model of Huntington's disease, a fatal neurodegenerative disorder characterized by accumulation of polyglutamine-containing aggregate formation in the brain. Furthermore, we showed that loss of NHE5 results in increased polyglutamine accumulation in an animal model of Huntington's disease. Our data suggest that cellular pH regulation by NHE1 and NHE5 plays a role in regulating basal autophagy and thereby promotes autophagy-mediated degradation of proteins including polyglutamine aggregates.Kazuya TogashiShuji WakatsukiAkiko FurunoShinji TokunagaYoshitaka NagaiToshiyuki ArakiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e81313 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kazuya Togashi Shuji Wakatsuki Akiko Furuno Shinji Tokunaga Yoshitaka Nagai Toshiyuki Araki Na+/H+ exchangers induce autophagy in neurons and inhibit polyglutamine-induced aggregate formation.
description	In polyglutamine diseases, an abnormally elongated polyglutamine results in protein misfolding and accumulation of intracellular aggregates. Autophagy is a major cellular degradative pathway responsible for eliminating unnecessary proteins, including polyglutamine aggregates. Basal autophagy constitutively occurs at low levels in cells for the performance of homeostatic function, but the regulatory mechanism for basal autophagy remains elusive. Here we show that the Na(+)/H(+) exchanger (NHE) family of ion transporters affect autophagy in a neuron-like cell line (Neuro-2a cells). We showed that expression of NHE1 and NHE5 is correlated to polyglutamine accumulation levels in a cellular model of Huntington's disease, a fatal neurodegenerative disorder characterized by accumulation of polyglutamine-containing aggregate formation in the brain. Furthermore, we showed that loss of NHE5 results in increased polyglutamine accumulation in an animal model of Huntington's disease. Our data suggest that cellular pH regulation by NHE1 and NHE5 plays a role in regulating basal autophagy and thereby promotes autophagy-mediated degradation of proteins including polyglutamine aggregates.
format	article
author	Kazuya Togashi Shuji Wakatsuki Akiko Furuno Shinji Tokunaga Yoshitaka Nagai Toshiyuki Araki
author_facet	Kazuya Togashi Shuji Wakatsuki Akiko Furuno Shinji Tokunaga Yoshitaka Nagai Toshiyuki Araki
author_sort	Kazuya Togashi
title	Na+/H+ exchangers induce autophagy in neurons and inhibit polyglutamine-induced aggregate formation.
title_short	Na+/H+ exchangers induce autophagy in neurons and inhibit polyglutamine-induced aggregate formation.
title_full	Na+/H+ exchangers induce autophagy in neurons and inhibit polyglutamine-induced aggregate formation.
title_fullStr	Na+/H+ exchangers induce autophagy in neurons and inhibit polyglutamine-induced aggregate formation.
title_full_unstemmed	Na+/H+ exchangers induce autophagy in neurons and inhibit polyglutamine-induced aggregate formation.
title_sort	na+/h+ exchangers induce autophagy in neurons and inhibit polyglutamine-induced aggregate formation.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/927628d3b37e4d47b4b246f92f5401d8
work_keys_str_mv	AT kazuyatogashi nahexchangersinduceautophagyinneuronsandinhibitpolyglutamineinducedaggregateformation AT shujiwakatsuki nahexchangersinduceautophagyinneuronsandinhibitpolyglutamineinducedaggregateformation AT akikofuruno nahexchangersinduceautophagyinneuronsandinhibitpolyglutamineinducedaggregateformation AT shinjitokunaga nahexchangersinduceautophagyinneuronsandinhibitpolyglutamineinducedaggregateformation AT yoshitakanagai nahexchangersinduceautophagyinneuronsandinhibitpolyglutamineinducedaggregateformation AT toshiyukiaraki nahexchangersinduceautophagyinneuronsandinhibitpolyglutamineinducedaggregateformation
_version_	1718421396202192896

Na+/H+ exchangers induce autophagy in neurons and inhibit polyglutamine-induced aggregate formation.

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