Abstract
RPE65, the retinal pigment epithelium (RPE) smooth endoplasmic reticulum (sER) membrane-associated retinoid isomerase, plays an indispensable role in sustaining visual function in vertebrates. An important aspect which has attracted considerable attention is the posttranslational modification by S-palmitoylation of RPE65. Some studies show that RPE65 is a palmitoylated protein, but others deny that conclusion. While it is considered to be mainly responsible for RPE65’s membrane association, we still lack conclusive evidence about RPE65 palmitoylation. In this review, we provide an overview of the history and current understanding of RPE65 palmitoylation.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Aicart-Ramos C, Valero RA, Rodriguez-Crespo I (2011) Protein palmitoylation and subcellular trafficking. Biochim Biophys Acta 1808:2981–2994
Bavik CO, Levy F, Hellman U et al (1993) The retinal pigment epithelial membrane receptor for plasma retinol-binding protein. Isolation and cDNA cloning of the 63-kDa protein. J Biol Chem 268:20540–20546
Bernstein PS, Law WC, Rando RR (1987) Biochemical characterization of the retinoid isomerase system of the eye. J Biol Chem 262:16848–16857
Chamberlain LH, Shipston MJ (2015) The physiology of protein S-acylation. Physiol Rev 95:341–376
De I, Sadhukhan S (2018) Emerging Roles of DHHC-mediated Protein S-palmitoylation in Physiological and Pathophysiological Context. Eur J Cell Biol 97:319–338
Golczak M, Kiser PD, Lodowski DT et al (2010) Importance of membrane structural integrity for RPE65 retinoid isomerization activity. J Biol Chem 285:9667–9682
Gonzalo S, Linder ME (1998) SNAP-25 palmitoylation and plasma membrane targeting require a functional secretory pathway. Mol Biol Cell 9:585–597
Greaves J, Chamberlain LH (2007) Palmitoylation-dependent protein sorting. J Cell Biol 176:249–254
Greaves J, Chamberlain LH (2011) DHHC palmitoyl transferases: substrate interactions and (patho)physiology. Trends Biochem Sci 36:245–253
Greaves J, Salaun C, Fukata Y et al (2008) Palmitoylation and membrane interactions of the neuroprotective chaperone cysteine-string protein. J Biol Chem 283:25014–25026
Hamel CP, Tsilou E, Pfeffer BA et al (1993a) Molecular cloning and expression of RPE65, a novel retinal pigment epithelium-specific microsomal protein that is post-transcriptionally regulated in vitro. J Biol Chem 268:15751–15757
Hamel CP, Tsilou E, Harris E et al (1993b) A developmentally regulated microsomal protein specific for the pigment epithelium of the vertebrate retina. J Neurosci Res 34:414–425
Jin M, Yuan Q, Li S et al (2007) Role of LRAT on the retinoid isomerase activity and membrane association of Rpe65. J Biol Chem 282:20915–20924
Jin M, Li S, Moghrabi WN et al (2005) Rpe65 is the retinoid isomerase in bovine retinal pigment epithelium. Cell 122:449–459
Kiser PD, Golczak M, Lodowski DT et al (2009) Crystal structure of native RPE65, the retinoid isomerase of the visual cycle. Proc Natl Acad Sci U S A 106:17325–17330
Kiser PD, Farquhar ER, Shi W et al (2012) Structure of RPE65 isomerase in a lipidic matrix reveals roles for phospholipids and iron in catalysis. Proc Natl Acad Sci U S A 109:E2747–E2756
Ma J, Zhang J, Othersen KL et al (2001) Expression, purification, and MALDI analysis of RPE65. Invest Ophthalmol Vis Sci 42:1429–1435
Magee AI, Gutierrez L, Marshall CJ et al (1989) Targeting of oncoproteins to membranes by fatty acylation. J Cell Sci Suppl 11:149–160
Moiseyev G, Chen Y, Takahashi Y et al (2005) RPE65 is the isomerohydrolase in the retinoid visual cycle. Proc Natl Acad Sci U S A 102:12413–12418
Nikolaeva O, Takahashi Y, Moiseyev G et al (2009) Purified RPE65 shows isomerohydrolase activity after reassociation with a phospholipid membrane. FEBS J 276:3020–3030
Redmond TM, Poliakov E, Yu S et al (2005) Mutation of key residues of RPE65 abolishes its enzymatic role as isomerohydrolase in the visual cycle. Proc Natl Acad Sci U S A 102:13658–13663
Redmond TM, Yu S, Lee E et al (1998) Rpe65 is necessary for production of 11-cis-vitamin A in the retinal visual cycle. Nat Genet 20:344–351
Sagara H, Hirosawa K (1991) Monoclonal antibodies which recognize endoplasmic reticulum in the retinal pigment epithelium. Exp Eye Res 53:765–771
Takahashi Y, Moiseyev G, Chen Y et al (2006) The roles of three palmitoylation sites of RPE65 in its membrane association and isomerohydrolase activity. Invest Ophthalmol Vis Sci 47:5191–5196
Takahashi Y, Moiseyev G, Ablonczy Z et al (2009) Identification of a novel palmitylation site essential for membrane association and isomerohydrolase activity of RPE65. J Biol Chem 284:3211–3218
Topinka JR, Bredt DS (1998) N-terminal palmitoylation of PSD-95 regulates association with cell membranes and interaction with K+ channel Kv1.4. Neuron 20:125–134
Tsilou E, Hamel CP, Yu S et al (1997) RPE65, the major retinal pigment epithelium microsomal membrane protein, associates with phospholipid liposomes. Arch Biochem Biophys 346:21–27
Xue L, Gollapalli DR, Maiti P et al (2004) A palmitoylation switch mechanism in the regulation of the visual cycle. Cell 117:761–771
Yuan Q, Kaylor JJ, Miu A et al (2010) Rpe65 isomerase associates with membranes through an electrostatic interaction with acidic phospholipid headgroups. J Biol Chem 285:988–999
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this paper
Cite this paper
Uppal, S., Poliakov, E., Gentleman, S., Redmond, T.M. (2019). RPE65 Palmitoylation: A Tale of Lipid Posttranslational Modification. In: Bowes Rickman, C., Grimm, C., Anderson, R., Ash, J., LaVail, M., Hollyfield, J. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 1185. Springer, Cham. https://doi.org/10.1007/978-3-030-27378-1_88
Download citation
DOI: https://doi.org/10.1007/978-3-030-27378-1_88
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-27377-4
Online ISBN: 978-3-030-27378-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)