Advertisement

On Your Marks… Get Bound… Internalize!

  • Ah-Lai Law
  • Emeline F. NandrotEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 723)

Abstract

Photoreceptor shedding and its phagocytosis by the retinal pigment epithelium is a crucial process in the renewal of the light-sensitive photoreceptor outer segments (POS). This internalization process shares many components used by macrophages in apoptotic cell clearance, but is unique in that this process is rhythmic. This chapter discusses the molecular mechanisms known so far to be involved in the journey of the POS that follows three sequential steps: particle recognition, binding, and internalization.

Keywords

Retinal pigment epithelium Photoreceptor outer segments Phagocytosis Daily rhythm αvβ5 integrin MFG-E8 FAK MerTK Annexin 2 

References

  1. Boesze-Battaglia K, Albert AD (1992) Phospholipid distribution among bovine rod outer segment plasma membrane and disk membranes. Exp Eye Res 54:821–823PubMedCrossRefGoogle Scholar
  2. Chaitin MH, Hall MO (1983) Defective ingestion of rod outer segments by cultured dystrophic rat pigment epithelial cells. Invest Ophthalmol Vis Sci 24:812–820PubMedGoogle Scholar
  3. Chang Y, Finnemann SC (2007) Tetraspanin CD81 is required for the alpha v beta5-integrin-dependent particle-binding step of RPE phagocytosis. J Cell Sci 120:3053–3063PubMedCrossRefGoogle Scholar
  4. D’Cruz PM, Yasumura D, Weir J et al (2000) Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat. Hum Mol Genet 9:645–651PubMedCrossRefGoogle Scholar
  5. Finnemann SC, Bonilha VL, Marmorstein AD et al (1997) Phagocytosis of rod outer segments by retinal pigment epithelial cells requires alpha(v)beta5 integrin for binding but not for internalization. Proc Natl Acad Sci USA 94:12932–12937PubMedCrossRefGoogle Scholar
  6. Finnemann SC, Rodriguez-Boulan E (1999) Macrophage and retinal pigment epithelium phagocytosis: apoptotic cells and photoreceptors compete for alphavbeta3 and alphavbeta5 integrins, and protein kinase C regulates alphavbeta5 binding and cytoskeletal linkage. J Exp Med 190:861–874PubMedCrossRefGoogle Scholar
  7. Finnemann SC, Silverstein RL (2001) Differential roles of CD36 and alphavbeta5 integrin in photoreceptor phagocytosis by the retinal pigment epithelium. J Exp Med 194:1289–1298PubMedCrossRefGoogle Scholar
  8. Finnemann SC (2003) Focal adhesion kinase signaling promotes phagocytosis of integrin-bound photoreceptors. EMBO J 22:4143–4154PubMedCrossRefGoogle Scholar
  9. Gibbs D, Kitamoto J, Williams DS (2003) Abnormal phagocytosis by retinal pigmented epithelium that lacks myosin VIIa, the Usher syndrome 1B protein. Proc Natl Acad Sci USA 100:6481–6486PubMedCrossRefGoogle Scholar
  10. de Graauw M, Tijdens I, Smeets MB et al (2008) Annexin A2 phosphorylation mediates cell scattering and branching morphogenesis via cofilin Activation. Mol Cell Biol 28:1029–1040PubMedCrossRefGoogle Scholar
  11. Hall MO, Prieto AL, Obin MS et al (2001) Outer segment phagocytosis by cultured retinal pigment epithelial cells requires Gas6. Exp Eye Res 73:509–520PubMedCrossRefGoogle Scholar
  12. Hall MO, Obin MS, Heeb MJ et al (2005) Both protein S and Gas6 stimulate outer segment phagocytosis by cultured rat retinal pigment epithelial cells. Exp Eye Res 81:581–591PubMedCrossRefGoogle Scholar
  13. Hall MO, Obin MS, Prieto AL et al (2002) Gas6 binding to photoreceptor outer segments requires gamma-carboxyglutamic acid (Gla) and Ca(2+) and is required for OS phagocytosis by RPE cells in vitro. Exp Eye Res 75:391–400PubMedGoogle Scholar
  14. Hanayama R, Tanaka M, Miwa K et al (2002) Identification of a factor that links apoptotic cells to phagocytes. Nature 417:182–187PubMedCrossRefGoogle Scholar
  15. Hayes MJ, Merrifield CJ, Shao D et al (2004) Annexin 2 binding to phosphatidylinositol 4,5-bisphosphate on endocytic vesicles is regulated by the stress response pathway. J Biol Chem 279:14157–14164PubMedCrossRefGoogle Scholar
  16. Hayes MJ, Moss SE (2009) Annexin 2 has a dual role as regulator and effector of v-Src in cell transformation. J Biol Chem 284:10202–10210PubMedCrossRefGoogle Scholar
  17. Hayes MJ, Shao D, Bailly M, Moss SE (2006) Regulation of actin dynamics by annexin 2. EMBO J 25:1816–1826PubMedCrossRefGoogle Scholar
  18. Heth CA, Marescalchi PA (1994) Inositol triphosphate generation in cultured rat retinal pigment epithelium. Invest Ophthalmol Vis Sci 35:409–416PubMedGoogle Scholar
  19. LaVail MM, Pinto LH, Yasumura D (1981) The interphotoreceptor matrix in rats with inherited retinal dystrophy. Invest Ophthalmol Vis Sci 21:658–668PubMedGoogle Scholar
  20. LaVail M (1976) Rod outer segment disk shedding in rat retina: relationship to cyclic lighting. Science 194:1071–1074PubMedCrossRefGoogle Scholar
  21. Law A, Ling Q, Hajjar KA et al (2009) Annexin A2 regulates phagocytosis of photoreceptor outer segments in the mouse retina. Mol Biol Cell 20:3896–3904PubMedCrossRefGoogle Scholar
  22. Nandrot E, Dufour EM, Provost AC et al (2000) Homozygous deletion in the coding sequence of the c-mer gene in RCS rats unravels general mechanisms of physiological cell adhesion and apoptosis. Neurobiol Dis 7:586–599PubMedCrossRefGoogle Scholar
  23. Nandrot EF, Anand M, Almeida D et al (2007) Essential role for MFG-E8 as ligand for alphavbeta5 integrin in diurnal retinal phagocytosis. Proc Natl Acad Sci USA 104:12005–12010PubMedCrossRefGoogle Scholar
  24. Nandrot EF, Anand M, Sircar M et al (2006) Novel role for alphavbeta5-integrin in retinal adhesion and its diurnal peak. Am J Physiol Cell Physiol 290:C1256–1262PubMedCrossRefGoogle Scholar
  25. Nandrot EF, Kim Y, Brodie SE et al (2004) Loss of synchronized retinal phagocytosis and age-related blindness in mice lacking alphavbeta5 integrin. J Exp Med 200:1539–1545PubMedCrossRefGoogle Scholar
  26. Nyberg P, He X, Härdig Y et al (1997) Stimulation of Sky tyrosine phosphorylation by bovine protein S--domains involved in the receptor-ligand interaction. Eur J Biochem 246:147–154PubMedCrossRefGoogle Scholar
  27. Prasad D, Rothlin CV, Burrola P et al (2006) TAM receptor function in the retinal pigment epithelium. Mol Cell Neurosci 33:96–108PubMedCrossRefGoogle Scholar
  28. Ryeom SW, Silverstein RL, Scotto A et al (1996a) Binding of anionic phospholipids to retinal ­pigment epithelium may be mediated by the scavenger receptor CD36. J Biol Chem 271:20536–20539PubMedCrossRefGoogle Scholar
  29. Ryeom SW, Sparrow JR, Silverstein RL (1996b) CD36 participates in the phagocytosis of rod outer segments by retinal pigment epithelium. J Cell Sci 109 (Pt 2):387–395PubMedGoogle Scholar
  30. Strick DJ, Feng W, Vollrath D (2009) Mertk drives myosin II redistribution during retinal pigment epithelial phagocytosis. Invest Ophthalmol Vis Sci 50:2427–2435PubMedCrossRefGoogle Scholar
  31. Vollrath D, Feng W, Duncan JL et al (2001) Correction of the retinal dystrophy phenotype of the RCS rat by viral gene transfer of Mertk. Proc Natl Acad Sci USA 98:12584–12589PubMedCrossRefGoogle Scholar
  32. Young RW, Bok D (1969) Participation of the retinal pigment epithelium in the rod outer segment renewal process. J Cell Biol 42:392–403PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.INSERM, U968ParisFrance
  2. 2.Genetics DepartmentUPMC Univ Paris 06, UMR_S 968, Institut de la VisionParisFrance
  3. 3.CNRS, UMR_7210ParisFrance

Personalised recommendations