Transmembrane proteins tetraspanin 4 and CD9 sense membrane curvature
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Abstract
Multiple membrane-shaping and remodeling processes are associated with tetraspanin proteins by yet unknown mechanisms. Tetraspanins constitute a family of proteins with four transmembrane domains present in every cell type. Prominent examples are tetraspanin4 and CD9, which are required for the fundamental cellular processes of migrasome formation and fertilization, respectively. These proteins are enriched in curved membrane structures, such as cellular retraction fibers and oocyte microvilli. The factors driving this enrichment are, however, unknown. Here, we revealed that tetraspanin4 and CD9 are curvature sensors with a preference for positive membrane curvature. To this end, we used a biomimetic system emulating membranes of cell retraction fibers and oocyte microvilli by membrane tubes pulled out of giant plasma membrane vesicles with controllable membrane tension and curvature. We developed a simple thermodynamic model for the partitioning of curvature sensors between flat and tubular membranes, which allowed us to estimate the individual intrinsic curvatures of the two proteins. Overall, our findings illuminate the process of migrasome formation and oocyte microvilli shaping and provide insight into the role of tetraspanin proteins in membrane remodeling processes.
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Proteomic landscape of tunneling nanotubes reveals CD9 and CD81 tetraspanins as key regulatorsPreprint
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Small-Molecule Modulators of Lipid Raft Stability and Protein-Raft PartitioningPreprint
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Membrane morphologies arising from multiconformational protein states
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Mutant KRAS Suppresses DNA Sensing by Remodeling Membrane Tension to Clear Extracellular Tumor DNA
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Self-citationEmerging roles of migrasomes in blood–tissue barrier integrity and intercellular signaling
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- Authors
- Dharan, R., Goren, S., Cheppali, S. K., Shendrik, P., Brand, G., Vaknin, A., Yu, L., Kozlov, M. M., & Sorkin, R.
- Affiliations
- Tel Aviv University (IL)
- Peking University (CN)
- Corresponding author
- Sorkin, Raya
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2022-10-17
- Volume
- 119
- Issue
- 43
- Pages
- e2208993119-e2208993119
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC9618112
- OpenAlex
- W4306642138
- Cited by
- 70
- References
- 38
- Citations by year
- 2026: 9 · 2025: 19 · 2024: 24 · 2023: 14 · 2022: 4
- FWCI
- 4.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Israel Science Foundation (1289/20, 3292/19)
- Ratner center for single molecule science (postdoctoral fellowship)
- Deutsche Forschungsgemeinschaft (SFB 958 "Scaffolding of Membranes")
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- CD9, membrane curvature sensing, membrane remodeling, membrane tubes, membrane tension, thermodynamic modeling, intrinsic curvature
- MeSH terms
- Cell Membrane, Microvilli, Oocytes, Tetraspanins, Tetraspanin 30, Tetraspanin 28, Tetraspanin 29
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