Opposite Roles of MerTK Ligands Gas6 and Protein S During Retinal Phagocytosis

Adv Exp Med Biol. 2018:1074:577-583. doi: 10.1007/978-3-319-75402-4_70.

Abstract

MerTK is required for photoreceptor outer segment (POS) phagocytosis by retinal pigment epithelial (RPE) cells, a diurnal function essential for vision maintenance. In vivo, MerTK is stimulated at the time of the phagocytic peak through an intracellular signaling pathway. However, MerTK ligands Gas6 and Protein S are expressed in both RPE cells and photoreceptors, and at least one of them required for phagocytosis to occur. Still, their exact role in the retina was not clear until recently. This review combines results from different studies to shed the light on a tissue-specific regulation of MerTK function by its ligands. Indeed, with opposite effects on RPE phagocytosis and changes in their expression levels around the time of POS uptake, Gas6 and Protein S may contribute to the tight control of the acute phagocytic peak in the retina.

Keywords: Circadian rhythm; Gas6; Ligands; MerTK; Phagocytosis; Photoreceptor outer segments; Protein S; Retinal pigment epithelium.

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Cells, Cultured
  • Circadian Rhythm
  • Enzyme Activation
  • Eye Proteins / metabolism*
  • Humans
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Ligands
  • Macrophages / metabolism
  • Mice
  • Phagocytosis / physiology*
  • Protein S / physiology*
  • Rats
  • Retina / cytology
  • Retina / metabolism*
  • Rod Cell Outer Segment / metabolism
  • Signal Transduction / physiology
  • c-Mer Tyrosine Kinase / deficiency
  • c-Mer Tyrosine Kinase / metabolism*
  • c-Mer Tyrosine Kinase / physiology

Substances

  • Eye Proteins
  • Intercellular Signaling Peptides and Proteins
  • Ligands
  • Protein S
  • growth arrest-specific protein 6
  • Mertk protein, mouse
  • Mertk protein, rat
  • c-Mer Tyrosine Kinase