Cited by 70Lipid Membrane Structure and BehaviorCell Adhesion Molecules ResearchCellular Mechanics and Interactions

Transmembrane proteins tetraspanin 4 and CD9 sense membrane curvature

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Dharan, Raviv, Goren, Shahar, Cheppali, Sudheer Kumar, Shendrik, Petr, Brand, Guy, Vaknin, Alisa, Yu, Li, Kozlov, Michael M. +1 more·2022·Proceedings of the National Academy of Sciences

Published version of a preprint

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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Crossref · 10.1073/pnas.2208993119

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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
Venue
Proceedings of the National Academy of Sciences
Published
2022-10-17
Volume
119
Issue
43
Pages
e2208993119-e2208993119
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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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