Abstract
The visual cycle is the complex enzymatic retinoid-processing involved in regenerating bleached rod and cone visual pigments.1 Central to visual cycle physiology is the cellular retinaldehyde-binding protein (CRALBP), a 36kDa cytosolic protein with high affinity for 11-cis-retinal and 11-cis-retinol. CRALBP is expressed in retinal pigment epithelium (RPE) and Müller cells, as well as in ciliary epithelium, iris, cornea, pineal gland and a subset of oligodendrocytes of the optic nerve and brain.2 Its function outside the RPE is not known, although a recent behavioral genetic study suggests that CRALBP may contribute to ethanol preference in mice.3 In the RPE, CRALBP serves as an 11-cis-retinol acceptor in the visual cycle isomerization step and as a substrate carrier for 11-cis-retinol dehydrogenase. 4–8 These functions require the rapid association and release of retinoid from the CRALBP ligand-binding pocket and involve critical protein interactions. To better understand the visual cycle, we are characterizing CRALBP ligand and protein interactions and retinoid trafficking within the RPE.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
T.D. Lamb & E.N. Pugh, Jr., Dark adaptation and the retinoid cycle of vision, Prog Retin Eye Res 23:307–80 (2004).
J.C. Saari, J. Huang, D.E. Possin, R.N. Fariss, J. Leonard, G.G. Garwin, J.W. Crabb & A.H. Milam, CRALBP is expressed by oligodendrocytes in optic nerve and brain, Glia 21:259–68 (1997).
J.A. Treadwell, K.B. Pagniello & S.M. Singh, Genetic segregation of brain gene expression identifies retinaldehyde binding protein 1 and syntaxin 12 as potential contributors to ethanol preference in mice, Behav Genet 34:425–39 (2004).
J.C. Saari, D.L. Bredberg & N. Noy, Control of substrate flow at a branch in the visual cycle, Biochemistry 33:3106–12 (1994).
J.C. Saari, M. Nawrot, B.N. Kennedy, G.G. Garwin, J.B. Hurley, J. Huang, D.E. Possin & J.W. Crabb, Visual cycle impairment in cellular retinaldehyde binding protein (CRALBP) knockout mice results in delayed dark adaptation, Neuron 29:739–48 (2001).
I. Golovleva, S. Bhattacharya, Z. Wu, N. Shaw, Y. Yang, K. Andrabi, K.A. West, M.S. Burstedt, K. Forsman, G. Holmgren, O. Sandgren, N. Noy, J. Qin & J.W. Crabb, Disease-causing mutations in CRALBP tighten and abolish ligand interactions, J Biol Chem 278:12397–402 (2003).
A. Winston & R.R. Rando, Regulation of isomerohydrolase activity in the visual cycle, Biochemistry 37:2044–2050 (1998).
H. Stecher, M.H. Gelb, J.C. Saari & K. Palczewski, Preferential release of 11-cis-retinol from retinal pigment epithelial cells in the presence of CRALBP, J Biol Chem 274:8577–85 (1999).
M.A. Maw, B. Kennedy, A. Knight, R. Bridges, K.E. Roth, E.J. Mani, J.K. Mukkadan, D. Nancarrow, J.W. Crabb & M.J. Denton, Mutation of the gene encoding cellular retinaldehyde-binding protein in autosomal recessive retinitis pigmentosa, Nat Genet 17:198–200 (1997).
M.S. Burstedt, O. Sandgren, G. Holmgren & K. Forsman-Semb, Bothnia dystrophy caused by mutations in the CRALBP gene (RLBP1) on chromosome 15q26, Invest Ophthalmol Vis Sci 40:995–1000 (1999).
H. Morimura, E.L. Berson & T.P. Dryja, Recessive mutations in the RLBP1 gene encoding cellular retinaldehyde-binding protein in a form of retinitis punctata albescens, Invest Ophthalmol Vis Sci 40:1000–4 (1999).
N. Katsanis, N.F. Shroyer, R.A. Lewis, J.C. Cavender, A.A. Al-Rajhi, M. Jabak & J.R. Lupski, Fundus albipunctatus and retinitis punctata albescens in a pedigree with an R150Q mutation in RLBP1, Clin Genet 59:424–9 (2001).
E.R. Eichers, J.S. Green, D.W. Stockton, C.S. Jackman, J. Whelan, J.A. McNamara, G.J. Johnson, J.R. Lupski & N. Katsanis, Newfoundland rod-cone dystrophy, an early-onset retinal dystrophy, is caused by splice-junction mutations in RLBP1, Am J Hum Genet 70:955–64 (2002).
J.W. Crabb, Z. Nie, Y. Chen, J.D. Hulmes, K.A. West, J.T. Kapron, S.E. Ruuska, N. Noy & J.C. Saari, Cellular retinaldehyde-binding protein ligand interactions. Gln-210 and Lys-221 are in the retinoid binding pocket, J Biol Chem 273:20712–20 (1998).
Z. Wu, Y. Yang, N. Shaw, S. Bhattacharya, L. Yan, K. West, K. Roth, N. Noy, J. Qin & J.W. Crabb, Mapping the ligand binding pocket in CRALBP, J Biol Chem 278:12390–6 (2003).
Z. Wu, A. Hasan, T. Liu, D. Teller, J.C. Saari, & J.W. Crabb, Identification of CRALBP Ligand Interactions by Photoaffinity Labeling, Hydrogen/Deuterium Exchange and Structural Modeling, J Biol Chem 279:27357–27364 (2004).
C. Panagabko, S. Morley, M. Hernandez, P. Cassolato, H. Gordon, R. Parsons, D. Manor & J. Atkinson, Ligand specificity in the CRAL-TRIO protein family, Biochemistry 42:6467–74 (2003).
J.W. Crabb, V.P. Gaur, G.G. Garwin, S.V. Marx, C. Chapline, C.M. Johnson & J.C. Saari, Topological and epitope mapping of CRALBP from retina, J Biol Chem 266:16674–83 (1991).
J.C. Saari & L. Bredberg, Enzymatic reduction of 11-cis-retinal bound to cellular retinal-binding protein, Biochim Biophys Acta 716:266–72 (1982).
M. Nawrot, K. West, J. Huang, D.E. Possin, A. Bretscher, J.W. Crabb & J.C. Saari, Cellular retinaldehyde-binding protein interacts with ERM-binding phosphoprotein 50 in retinal pigment epithelium, Invest Ophthalmol Vis Sci 45:393–401 (2004).
S.K. Bhattacharya, Z. Wu, Z. Jin, L. Yan, M. Miyagi, K. West, M. Nawrot, J.C. Saari & J.W. Crabb. Proteomic Approach to Identification of a Mammalian Visual Cycle Protein Complex. in Experimental Biology 2002 Vol. 16: A14 (FASEB J, New Orleans, LA, 2002).
N.L. Mata, E.T. Villazanna & A.T.C. Tsin, Colocalization of 11-cis retinyl esters and retinyl ester hydrolase activity in retinal pigment epithelium plasma membrane, Invest Ophthal Visual Sci 39:1312–19 (1998).
V.L. Bonilha, S.K. Bhattacharya, K.A. West, J.S. Crabb, J. Sun, M.E. Rayborn, M. Nawrot, J.C. Saari & J.W. Crabb, Support For a Proposed Retinoid-Processing Protein Complex in Apical Retinal Pigment Epithelium, Exp Eye Res 79:419–22 (2004).
V.L. Bonilha, S.K. Bhattacharya, K.A. West, J. Sun, J.W. Crabb, M.E. Rayborn & J.G. Hollyfield, Proteomic Characterization of Isolated Retinal Pigment Epithelium Microvilli, Mol Cell. Proteomics 3:1119–27 (2004).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Springer Science+Business Media, Inc.
About this paper
Cite this paper
Wu, Z. et al. (2006). CRALBP Ligand and Protein Interactions. In: Hollyfield, J.G., Anderson, R.E., LaVail, M.M. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 572. Springer, Boston, MA. https://doi.org/10.1007/0-387-32442-9_66
Download citation
DOI: https://doi.org/10.1007/0-387-32442-9_66
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-387-28464-4
Online ISBN: 978-0-387-32442-5
eBook Packages: MedicineMedicine (R0)