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...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2013-01-01
|
Series: | PLoS ONE |
Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24278418/?tool=EBI |
id |
doaj-927628d3b37e4d47b4b246f92f5401d8 |
---|---|
record_format |
Article |
spelling |
doaj-927628d3b37e4d47b4b246f92f5401d82021-03-04T10:13:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01811e8131310.1371/journal.pone.0081313Na+/H+ exchangers induce autophagy in neurons and inhibit polyglutamine-induced aggregate formation.Kazuya TogashiShuji WakatsukiAkiko FurunoShinji TokunagaYoshitaka NagaiToshiyuki ArakiIn 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24278418/?tool=EBI |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kazuya Togashi Shuji Wakatsuki Akiko Furuno Shinji Tokunaga Yoshitaka Nagai Toshiyuki Araki |
spellingShingle |
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. PLoS ONE |
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) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
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. |
url |
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24278418/?tool=EBI |
work_keys_str_mv |
AT kazuyatogashi nahexchangersinduceautophagyinneuronsandinhibitpolyglutamineinducedaggregateformation AT shujiwakatsuki nahexchangersinduceautophagyinneuronsandinhibitpolyglutamineinducedaggregateformation AT akikofuruno nahexchangersinduceautophagyinneuronsandinhibitpolyglutamineinducedaggregateformation AT shinjitokunaga nahexchangersinduceautophagyinneuronsandinhibitpolyglutamineinducedaggregateformation AT yoshitakanagai nahexchangersinduceautophagyinneuronsandinhibitpolyglutamineinducedaggregateformation AT toshiyukiaraki nahexchangersinduceautophagyinneuronsandinhibitpolyglutamineinducedaggregateformation |
_version_ |
1714806600472985600 |