Cytosolic transmembrane helices enter the ER membrane through EMC6-driven electrostatic interactions

Clicks: 19
ID: 320115
2026
Free PDF
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Emerging

Ranked #42 of 56 articles by views in journal of molecular cell biology

Most read Least read

Bar heights use a square-root scale.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
The endoplasmic reticulum membrane protein complex (EMC) facilitates transmembrane domain (TMD) insertion and translocation of small terminal domains. Here, we identify EMC as a critical determinant of epithelial sodium channel (ENaC) biosynthesis. EMC loss reduces ENaC expression without affecting surface trafficking, indicating a biosynthetic stabilizing role. We demonstrate that electrostatic interactions between the negatively charged distal segment of ENaC's TMD2 and a positively charged patch on EMC6 are essential for ENaC-EMC association. We propose a 'semi-insertase' mechanism wherein the Sec61 translocon partially inserts TMD2, leaving its hydrophilic distal segment exposed to the cytosol. EMC captures this segment through electrostatic attraction and completes membrane integration. Bioinformatic analysis identified a group of non-canonical EMC clients including >200 multipass proteins with similarly charged TMDs, suggesting that electrostatic capture may represent a solution for inserting unconventional hydrophilic transmembrane segments. Additionally, we demonstrate that EMC8 plays an essential role in stabilizing the EMC-a function that cannot be compensated by its homolog EMC9 due to lower expression and absence of compensatory upregulation in EMC8-deficient cells. These results reveal a multifaceted EMC mechanism coupling insertase activity with chaperone-like stabilization to facilitate biogenesis of multipass membrane proteins containing highly hydrophilic TMDs.
Reference Key
openalex_W7167598061 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Hongyan Zheng, Wenxue Gu, Tong Zhou, C M Canessa
Journal journal of molecular cell biology
Year 2026
DOI
10.1093/jmcb/mjag021
URL
https://doi.org/10.1093/jmcb/mjag021
Keywords Keywords not found

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.