Related Experiment Video
Updated: Jul 6, 2026
Establishment of Epstein-Barr Virus Growth-transformed Lymphoblastoid Cell Lines
Published on: November 8, 2011
Epstein-Barr Virus LMP1 Modulates the CD63 Interactome
Mujeeb Cheerathodi1, Dingani Nkosi1, Allaura S Cone1
1Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, USA.
Insights
The CD63 protein
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Tetraspanin CD63 is a cell surface protein involved in protein trafficking and extracellular vesicle (EV) formation.
- CD63 plays a role in the trafficking of LMP1 (latent membrane protein 1) to EVs, influencing intracellular signaling pathways.
- Understanding the CD63 interactome is crucial for elucidating its role in cellular processes.
Purpose of the Study:
- To comprehensively identify proteins interacting with CD63 using BioID and mass spectrometry.
- To investigate how LMP1 modulates the CD63 protein interaction network.
- To explore the functional implications of these interactions on cellular signaling and trafficking.
Main Methods:
- Utilized the BioID proximity labeling method combined with mass spectrometry to map the CD63 interactome.
- Performed biological process enrichment analysis on identified protein networks.
- Investigated the interaction of LMP1 with CD63 and its associated proteins, including signaling molecules.
Main Results:
- Identified a network of 1600 proteins proximal to CD63, enriched in signal transduction, cell communication, and protein transport.
- The CD63 interactome included Rab GTPases, SNARE proteins, and sorting nexins.
- LMP1 altered the CD63 interactome, shifting enrichment from protein localization to metabolic processes and translation, and revealed interactions with mTOR, Nedd4 L, and PP2A.
Conclusions:
- LMP1 significantly modifies the CD63 protein network, impacting cellular processes.
- The findings provide insights into the multiprotein complex formation involving CD63, LMP1, mTOR, Nedd4 L, and PP2A.
- This study enhances understanding of the molecular mechanisms underlying endocytic trafficking and extracellular vesicle cargo sorting and secretion.
Abstract:
Tetraspanin CD63 is a cluster of cell surface proteins with four transmembrane domains; it is associated with tetraspanin-enriched microdomains and typically localizes to late endosomes and lysosomes. CD63 plays an important role in the cellular trafficking of different proteins, EV cargo sorting, and vesicle formation. We have previously shown that CD63 is important in LMP1 trafficking to EVs, and this also affects LMP1-mediated intracellular signaling including MAPK/ERK, NF-κB, and mTOR activation. Using the BioID method combined with mass spectrometry, we sought to define the broad CD63 interactome and how LMP1 modulates this network of interacting proteins. We identified a total of 1600 total proteins as a network of proximal interacting proteins to CD63. Biological process enrichment analysis revealed significant involvement in signal transduction, cell communication, protein metabolism, and transportation. The CD63-only interactome was enriched in Rab GTPases, SNARE proteins, and sorting nexins, while adding LMP1 into the interactome increased the presence of signaling and ribosomal proteins. Our results showed that LMP1 alters the CD63 interactome, shifting the network of protein enrichment from protein localization and vesicle-mediated transportation to metabolic processes and translation. We also show that LMP1 interacts with mTOR, Nedd4 L, and PP2A, indicating the formation of a multiprotein complex with CD63, thereby potentially regulating LMP1-dependent mTOR signaling. Collectively, the comprehensive analysis of CD63 proximal interacting proteins provides insights into the network of partners required for endocytic trafficking and extracellular vesicle cargo sorting, formation, and secretion.
Related Concept Videos
02:23Abnormal Proliferation
01:19Inhibitors of Virion Maturation and Assembly