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TAM receptor function in the retinal pigment epithelium

Dipti Prasad1, Carla Vanina Rothlin, Patrick Burrola

  • 1Molecular Neurobiology Laboratory, The Salk Institute, 10010 N. Torrey Pines Rd., La Jolla, CA 92037, USA.

Molecular and Cellular Neurosciences
|August 12, 2006
PubMed

Insights

Retinal pigment epithelium (RPE) cells require TAM receptors Mer and Tyro 3, activated by Protein S, not Gas6, for photoreceptor outer segment phagocytosis and vision. Loss of Mer impacts Tyro 3, highlighting their interconnected roles.

Area of Science:

  • Ophthalmology
  • Cell Biology
  • Genetics

Background:

  • The TAM receptor tyrosine kinase Mer is crucial for retinal pigment epithelium (RPE) function.
  • Mer deficiency in RPE cells impairs photoreceptor outer segment phagocytosis, leading to photoreceptor degeneration and blindness.
  • Gas6 was previously thought to be the primary ligand for Mer in this process.

Purpose of the Study:

  • To investigate the specific TAM receptor ligands involved in RPE function and photoreceptor maintenance.
  • To clarify the role of Gas6 and identify alternative ligands in the Mer-mediated phagocytosis pathway.
  • To understand the interplay between different TAM receptors in RPE cells.

Main Methods:

  • Utilized Gas6 mutant mice to assess the in vivo necessity of Gas6 for RPE function.
  • Examined RPE cells for the expression of other TAM receptors, specifically Tyro 3.
  • Investigated the activation of Mer and Tyro 3 by Protein S in RPE cells.
  • Analyzed the expression levels of Tyro 3 in Mer-deficient RPE cells.

Main Results:

  • Gas6 mutant mice exhibited histologically normal retinas, indicating Gas6 is not essential for RPE function.
  • RPE cells express both Mer and Tyro 3 receptors.
  • Protein S, a Gas6-related ligand, activates both Mer and Tyro 3 receptors in RPE cells.
  • Loss of Mer function led to a significant downregulation of Tyro 3 expression.

Conclusions:

  • Protein S, not Gas6, is the relevant ligand for TAM receptors Mer and Tyro 3 in mouse RPE cells.
  • Both Mer and Tyro 3 receptors are essential for RPE function and photoreceptor health.
  • Mer and Tyro 3 signaling pathways are interconnected in RPE cells, with Mer influencing Tyro 3 expression.

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