THE ROLE OF PHOSPHOLIPID SCRAMBLASES IN AUTOIMMUNE TISSUE DAMAGE: MECHANISMS OF PHOSPHATIDYLSERINE EXPOSURE AND IMMUNE ACTIVATION

Authors

  • Madina Umarova

    Student of the Faculty of General Medicine, Tashkent State Medical University, Tashkent, Uzbekistan

    Author

  • Islomjon Izbasarov

    Student of the Faculty of General Medicine, Tashkent State Medical University, Tashkent, Uzbekistan

    Author

  • Pokizaxon Nurillayeva

    Student of the Faculty of General Medicine, Tashkent State Medical University, Tashkent, Uzbekistan

    Author

  • Utkiraliyeva Umida

    Student of the Faculty of General Medicine, Tashkent State Medical University, Tashkent, Uzbekistan

    Author

  • Yoldoshovа Dilnozа Dаvronbek qizi

    Student of Group 202, Fаculty of Treаtment No. 2, Tаshkent Stаte Medicаl University, Tаshkent, Uzbekistаn

    Author

Keywords:
Phospholipid scramblases,phosphatidylserine externalization, TMEM16F, apoptosis, autoimmune diseases, tissue inflammation,immune dysregulation, efferocytosis
Abstract

Phospholipid scramblases are membrane proteins that disrupt lipid asymmetry, crucially exposing phosphatidylserine (PS) on the cell surface. Three major human scramblase families – the phospholipid scramblases (PLSCR), the TMEM16/anoctamin family, and the XKR (XK-related) family – have been characterized. PLSCR proteins (especially PLSCR1) were initially identified as Ca^2+-dependent scramblases, but their physiological role remains debated. TMEM16F (ANO6) is a Ca^2+-activated ion channel/scramblase essential for rapid PS externalization, as shown by TMEM16F knockout models and in Scott syndrome (a bleeding disorder). XKR family members (notably XKR8) are caspase-activated scramblases that irreversibly externalize PS during apoptosis. In apoptosis, scramblases mediate the hallmark PS “eat-me” signal for phagocytic clearance. Dysregulated scramblase activity or apoptotic clearance can trigger autoimmunity: for example, XKR8 deficiency in mice causes lupus-like disease, and human systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) patients exhibit altered scramblase expression and PS exposure. Here, we review recent biochemical and immunological studies of PLSCR, TMEM16, and XKR proteins, focusing on their lipid-translocation mechanisms, roles in apoptotic PS exposure, and links to autoimmunity (SLE, APS). We emphasize advances from the last decade and analyze how aberrant PS scrambling contributes to inflammatory diseases.

References

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Published
2026-03-12
Issue
Vol. 2 No. 3 (2026)
Section
Articles
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This work is licensed under a Creative Commons Attribution 4.0 International License.

How to Cite

THE ROLE OF PHOSPHOLIPID SCRAMBLASES IN AUTOIMMUNE TISSUE DAMAGE: MECHANISMS OF PHOSPHATIDYLSERINE EXPOSURE AND IMMUNE ACTIVATION. (2026). Eureka Journal of Health Sciences & Medical Innovation, 2(3), 86-99. https://eurekaoa.com/index.php/5/article/view/593

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