Mutant SOD1 inhibits ER-Golgi transport in amyotrophic lateral sclerosis

Atkin, Julie D., Farg, Manal A., Soo, Kai Ying, Walker, Adam K., Halloran, Mark, Turner, Bradley J., Nagley, Phillip and Horne, Malcolm K. (2014) Mutant SOD1 inhibits ER-Golgi transport in amyotrophic lateral sclerosis. Journal of Neurochemistry, 129 1: 190-204. doi:10.1111/jnc.12493

Author Atkin, Julie D.
Farg, Manal A.
Soo, Kai Ying
Walker, Adam K.
Halloran, Mark
Turner, Bradley J.
Nagley, Phillip
Horne, Malcolm K.
Title Mutant SOD1 inhibits ER-Golgi transport in amyotrophic lateral sclerosis
Journal name Journal of Neurochemistry   Check publisher's open access policy
ISSN 1471-4159
Publication date 2014-04-01
Sub-type Article (original research)
DOI 10.1111/jnc.12493
Open Access Status Not yet assessed
Volume 129
Issue 1
Start page 190
End page 204
Total pages 15
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Abstract Cu/Zn-superoxide dismutase is misfolded in familial and sporadic amyotrophic lateral sclerosis, but it is not clear how this triggers endoplasmic reticulum (ER) stress or other pathogenic processes. Here, we demonstrate that mutant SOD1 (mSOD1) is predominantly found in the cytoplasm in neuronal cells. Furthermore, we show that mSOD1 inhibits secretory protein transport from the ER to Golgi apparatus. ER-Golgi transport is linked to ER stress, Golgi fragmentation and axonal transport and we also show that inhibition of ER-Golgi trafficking preceded ER stress, Golgi fragmentation, protein aggregation and apoptosis in cells expressing mSOD1. Restoration of ER-Golgi transport by over-expression of coatomer coat protein II subunit Sar1 protected against inclusion formation and apoptosis, thus linking dysfunction in ER-Golgi transport to cellular pathology. These findings thus link several cellular events in amyotrophic lateral sclerosis into a single mechanism occurring early in mSOD1 expressing cells.
Keyword Amyotrophic lateral sclerosis
ER-Golgi transport
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
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