The HSP70 co-chaperone DNAJC14 targets misfolded pendrin for unconventional protein secretion

DSpace/Manakin Repository

The HSP70 co-chaperone DNAJC14 targets misfolded pendrin for unconventional protein secretion

Citable link to this page

 

 
Title: The HSP70 co-chaperone DNAJC14 targets misfolded pendrin for unconventional protein secretion
Author: Jung, Jinsei; Kim, Jiyoon; Roh, Shin Hye; Jun, Ikhyun; Sampson, Robert D.; Gee, Heon Yung; Choi, Jae Young; Lee, Min Goo

Note: Order does not necessarily reflect citation order of authors.

Citation: Jung, Jinsei, Jiyoon Kim, Shin Hye Roh, Ikhyun Jun, Robert D. Sampson, Heon Yung Gee, Jae Young Choi, and Min Goo Lee. 2016. “The HSP70 co-chaperone DNAJC14 targets misfolded pendrin for unconventional protein secretion.” Nature Communications 7 (1): 11386. doi:10.1038/ncomms11386. http://dx.doi.org/10.1038/ncomms11386.
Full Text & Related Files:
Abstract: Mutations in SLC26A4, which encodes pendrin, are responsible for hearing loss with an enlarged vestibular aqueduct and Pendred syndrome. The most prevalent mutation in East Asia is p.H723R (His723Arg), which leads to defects in protein folding and cell-surface expression. Here we show that H723R-pendrin can be rescued to the cell surface by an HSP70 co-chaperone DNAJC14-dependent unconventional trafficking pathway. Blockade of ER-to-Golgi transport or activation of ER stress signals induced Golgi-independent cell-surface expression of H723R-pendrin and restored its cell-surface Cl−/HCO3− exchange activity. Proteomic and short interfering RNA screenings with subsequent molecular analyses showed that Hsc70 and DNAJC14 are required for the unconventional trafficking of H723R-pendrin. Moreover, DNAJC14 upregulation was able to induce the unconventional cell-surface expression of H723R-pendrin. These results indicate that Hsc70 and DNAJC14 play central roles in ER stress-associated unconventional protein secretion and are potential therapeutic targets for diseases such as Pendred syndrome, which arise from transport defects of misfolded proteins.
Published Version: doi:10.1038/ncomms11386
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848490/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:27320315
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters