Transmembrane proteins tetraspanin 4 and CD9 sense membrane curvature

Raviv Dharan, Shahar Goren, Sudheer Kumar Cheppali, Petr Shendrik, Guy Brand, Alisa Vaknin, Li Yu, Michael M. Kozlov, Raya Sorkin

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article numbere2208993119
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number43
StatePublished - 25 Oct 2022


  • membrane curvature
  • migrasomes
  • optical tweezers
  • tetraspanin


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