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Updated: Feb 19, 2026

Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes
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Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes

Published on: March 14, 2021

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Context-dependent compensation among phosphatidylserine-recognition receptors

Kristen K Penberthy1,2, Claudia Rival1,2,3, Laura S Shankman1,2

  • 1Center for Cell Clearance, University of Virginia, Charlottesville, VA, USA.

Scientific Reports
|November 9, 2017
PubMed

Insights

Phosphatidylserine (PtdSer) receptors like MerTK are crucial for clearing apoptotic cells. Overexpressing BAI1 compensates for MerTK loss in testes but not the eye, showing context-dependent phagocytic receptor function.

Area of Science:

  • Immunology
  • Cell Biology
  • Ophthalmology

Background:

  • Phagocytes utilize multiple phosphatidylserine (PtdSer) receptors to recognize and clear apoptotic cells.
  • The specific roles and interchangeability of these PtdSer receptors in vivo remain largely unknown.
  • Loss of MerTK, a key PtdSer receptor, leads to apoptotic cell accumulation in testes and photoreceptor degeneration in the eye due to impaired phagocytosis.

Purpose of the Study:

  • To investigate whether the PtdSer receptor BAI1 can compensate for the loss of MerTK in vivo.
  • To determine the tissue-specific functional differences between MerTK and BAI1 in apoptotic cell clearance.
  • To elucidate the molecular mechanisms underlying MerTK's critical role in retinal pigmented epithelium (RPE) function.

Main Methods:

  • Overexpression of the PtdSer receptor BAI1 in MerTK-deficient (Mertk-/-) mice (Mertk-/- Bai1Tg).
  • Assessment of apoptotic germ cell clearance in testes and photoreceptor degeneration in the eye.
  • Analysis of visual cycle intermediates and unbiased RNA sequencing (RNAseq) of RPE from Mertk+/+ and Mertk-/- mice.

Main Results:

  • BAI1 overexpression rescued the clearance of apoptotic germ cells in the testes of Mertk-/- mice.
  • BAI1 overexpression failed to rescue RPE phagocytosis or prevent photoreceptor degeneration in Mertk-/- mice.
  • Mertk-/- mice exhibited dysregulation of genes involved in phagocytosis, metabolism, and retinal disease, even before photoreceptor degeneration onset.

Conclusions:

  • Phagocytic receptors are not functionally interchangeable; their compensatory roles are context- and tissue-dependent.
  • MerTK plays a critical, non-redundant role in RPE phagocytosis and retinal health.
  • Dysregulation of specific gene networks in MerTK-deficient RPE contributes to photoreceptor degeneration.

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