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Cell surface remodeling caused by the loss of the flippase subunit TMEM30A in immune cells

Cenk O Gurdap1, Franziska Ragaller1, Marion Muller2,3

  • 1Science for Life Laboratory, Department of Women's and Children's Health, Karolinska Institutet, Tomtebodavägen 23, 17165 Solna, Sweden.

Journal of Cell Science
|August 14, 2026
PubMed

Insights

Loss of TMEM30A disrupts plasma membrane lipid asymmetry, causing phosphatidylserine externalization and altered cell surface dynamics. This impacts immune cell function and may influence cancer immune evasion and therapy response.

Area of Science:

  • Cell Biology
  • Biophysics
  • Immunology

Background:

  • Plasma membrane lipid asymmetry is crucial for cell physiology, maintained by flippase enzymes like P4-ATPases.
  • TMEM30A, a P4-ATPase β-subunit, regulates phosphatidylserine (PS) asymmetry; its loss causes PS externalization, linked to diseases like lymphoma and immune evasion.

Purpose of the Study:

  • To systematically define the biophysical and molecular consequences of TMEM30A deletion in immune cells.
  • To investigate the impact of TMEM30A loss on membrane dynamics, surface protein composition, and glycocalyx structure.

Main Methods:

  • Utilized live-cell lipid reporters and membrane order probes to assess membrane properties.
  • Employed surface proteome mapping to analyze changes in cell surface proteins.
  • Investigated glycocalyx remodeling through the analysis of transmembrane mucin shedding.

Main Results:

  • TMEM30A-knockout cells exhibited significant phosphatidylserine externalization.
  • Observed increased lateral diffusion of membrane constituents and decreased plasma membrane order.
  • Identified reorganization of surface proteins, including increased tetraspanins and CD47, and ADAM10-dependent shedding of mucins like CD43 and CD162.

Conclusions:

  • TMEM30A loss induces coordinated reorganization of lipids, glycans, and proteins, linking flippase dysfunction to increased plasma membrane dynamics.
  • These findings suggest potential mechanisms for TMEM30A's role in disease and sensitization to immune therapy.
  • The study provides a surfaceome framework for understanding TMEM30A's clinical relevance in cancer.
Keywords:
ADAM10CD162CD43CD47CDC50AImmune evasionLipid asymmetryMembrane orderMucin sheddingPhosphatidylserine

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