![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Preprint)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
1MB |
Preview |
PDF (Supplementary Material)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
582kB |
| Item Type: | Preprint |
|---|---|
| Title: | Cell surface remodeling caused by the loss of TMEM30A in immune cells |
| Creators Name: | Gurdap, Cenk O., Ragaller, Franziska, Muller, Marion, Sjule, Ellen, Sych, Taras, Blomén, Linnea, Thoren, Fredrik, Levental, Ilya, Levental, Kandice R., Sattentau, Quentin and Sezgin, Erdinc |
| Abstract: | Plasma membrane lipid asymmetry is tightly regulated and fundamental to mammalian cell physiology. TMEM30A is the β-subunit of P4-ATPases, flippase enzymes that maintain strict phosphatidylserine (PS) asymmetry by pumping it from the outer to the cytosolic leaflet. Loss of TMEM30A function causes constitutive PS externalization and has been implicated in diseases such as diffuse large B-cell lymphoma and tumour immune evasion. Here, we systematically define the biophysical and molecular consequences of TMEM30A deletion in transformed immune cells. Using live-cell lipid reporters, membrane order probes and surface proteome mapping, we show that TMEM30A-knockout cells display robust PS externalization accompanied by faster lateral diffusion of membrane constituents and decreased plasma membrane order. Surface proteome reorganization includes increased abundance of tetraspanins and CD47. Further, TMEM30A loss triggers glycocalyx remodeling via ADAM10-dependent shedding that removes major mucins, including CD43 and CD162. Together, these data reveal a coordinated reorganization of lipids, glycans, and proteins upon TMEM30A loss that mechanistically links flippase dysfunction to immune evasion, increased plasma membrane dynamics and sensitization to anti-CD47 therapy. Moreover, Furthermore, our study provides an integrated surfaceome framework that illuminates the relationship between TMEM30A expression and clinical outcomes in cancer. |
| Keywords: | TMEM30A/CDC50A, Phosphatidylserine, Lipid Asymmetry, ADAM10, Mucin Shedding, CD43, CD162, Tetraspanins, CD47, Molecular Pixelation, Membrane Order, Lateral Diffusion, Immune Evasion, DLBCL, Fluorescence Correlation Spectroscopy, Pro12A |
| Source: | bioRxiv |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Article Number: | 2026.02.21.707187 |
| Date: | 23 February 2026 |
| Official Publication: | https://doi.org/10.64898/2026.02.21.707187 |
Repository Staff Only: item control page
