A novel ER J-protein DNAJB12 accelerates ER-associated degradation of membrane proteins including CFTR.

Yo hei Yamamoto, Taiji Kimura, Shuku Momohara, Masato Takeuchi, Tokio Tani, Yukio Kimata, Hiroshi Kadokura, Kenji Kohno

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Cytosolic Hsc70/Hsp70 are known to contribute to the endoplasmic reticulum (ER)-associated degradation of membrane proteins. However, at least in mammalian cells, its partner ER-localized J-protein for this cellular event has not been identified. Here we propose that this missing protein is DNAJB12. Protease protection assay and immunofluorescence study revealed that DNAJB12 is an ER-localized single membrane-spanning protein carrying a J-domain facing the cytosol. Using co-immunoprecipitation assay, we found that DNAJB12 is able to bind Hsc70 and thus can recruit Hsc70 to the ER membrane. Remarkably, cellular overexpression of DNAJB12 accelerated the degradation of misfolded membrane proteins including cystic fibrosis transmembrane conductance regulator (CFTR), but not a misfolded luminal protein. The DNAJB12-dependent degradation of CFTR was compromised by a proteasome inhibitor, lactacystin, suggesting that this process requires the ubiquitin-proteasome system. Conversely, knockdown of DNAJB12 expression attenuated the degradation of CFTR. Thus, DNAJB12 is a novel mammalian ER-localized J-protein that plays a vital role in the quality control of membrane proteins.

Original languageEnglish
Pages (from-to)107-116
Number of pages10
JournalCell structure and function
Volume35
Issue number2
DOIs
Publication statusPublished - 2010 Dec 23

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    Yamamoto, Y. H., Kimura, T., Momohara, S., Takeuchi, M., Tani, T., Kimata, Y., Kadokura, H., & Kohno, K. (2010). A novel ER J-protein DNAJB12 accelerates ER-associated degradation of membrane proteins including CFTR. Cell structure and function, 35(2), 107-116. https://doi.org/10.1247/csf.10023