A novel domain within the CIL regulates egress of IFITM3 from the Golgi and reveals a regulatory role of IFITM3 on the secretory pathway.

Abstract

The InterFeron-Induced TransMembrane proteins (IFITMs) are members of the dispanin/CD225 family that act as broad viral inhibitors by preventing viral-to-cellular membrane fusion. In this study, we uncover egress from the Golgi as an important step in the biology of IFITM3 by identifying the domain that regulates this process and that similarly controls the egress of the dispanins IFITM1 and PRRT2, protein linked to paroxysmal kinesigenic dyskinesia. In the case of IFITM3, high levels of expression of wild-type, or mutations in the Golgi egress domain, lead to accumulation of IFITM3 in the Golgi and drive generalized glycoprotein trafficking defects. These defects can be relieved upon incubation with Amphotericin B, compound known to relieve IFITM-driven membrane fusion defects, as well as by v-SNARE overexpression, suggesting that IFITM3 interferes with membrane fusion processes important for Golgi functionalities. The comparison of glycoprotein trafficking in WT versus IFITMs-KO cells indicates that the modulation of the secretory pathway is a novel feature of IFITM proteins. Overall, our study defines a novel domain that regulates the egress of several dispanin/CD225 members from the Golgi and identifies a novel modulatory function for IFITM3.

• Authors: Li Zhong, Yuxin Song, Federico Marziali, Rustem Uzbekov, Xuan-Nhi Nguyen, Chloé Journo, Philippe Roingeard, Andrea Cimarelli
• Journal: Life science alliance (Life Sci Alliance) Vol. 5 Issue 7 (07 2022) ISSN: 2575-1077 [Electronic] United States
• PMID: 35396335 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 Zhong et al.

Chemical References

• Membrane Proteins
• RNA-Binding Proteins

Topics

• Membrane Proteins (metabolism)
• RNA-Binding Proteins (metabolism)
• Secretory Pathway
• Virus Internalization