Abstract
Mutations in the gene Crumbs homolog 1 (CRB1) are responsible for several retinopathies that are diverse in severity and phenotype. Thus, there is considerable incentive to determine how disruption of this gene causes disease. Progress on this front will aid in developing molecular diagnostics that can predict disease severity with the ultimate goal of developing therapies for CRB1 retinopathies via gene replacement. The purpose of this review is to summarize what is known regarding CRB1 and highlights information outstanding. Doing so will provide a framework toward a thorough understanding of CRB1 at the molecular and protein level with the ultimate goal of deciphering how it contributes to the disease.
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References
Aleman TS, Cideciyan AV, Aguirre GK et al (2011) Human CRB1-associated retinal degeneration: comparison with the rd8 Crb1-mutant mouse model. Invest Ophthalmol Vis Sci 52:6898–6910
Alves CH, Pellissier LP, Wijnholds J (2014) The CRB1 and adherens junction complex proteins in retinal development and maintenance. Prog Retin Eye Res 40:35–52
Bujakowska K, Audo I, Mohand-Said S et al (2012) CRB1 mutations in inherited retinal dystrophies. Hum Mutat 33:306–315
den Hollander AI, Roepman R, Koenekoop RK et al (2008) Leber congenital amaurosis: genes, proteins and disease mechanisms. Prog Retin Eye Res 27:391–419
den Hollander AI, Johnson K, de Kok YJ et al (2001a) CRB1 has a cytoplasmic domain that is functionally conserved between human and Drosophila. Hum Mol Genet 10:2767–2773
den Hollander AI, Davis J, van der Velde-Visser SD et al (2004) CRB1 mutation spectrum in inherited retinal dystrophies. Hum Mutat 24:355–369
den Hollander AI, Heckenlively JR, van den Born LI et al (2001b) Leber congenital amaurosis and retinitis pigmentosa with Coats-like exudative vasculopathy are associated with mutations in the crumbs homologue 1 (CRB1) gene. Am J Hum Genet 69:198–203
den Hollander AI, ten Brink JB, de Kok YJ et al (1999) Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12). Nat Genet 23:217–221
Hoshino A, Ratnapriya R, Brooks MJ et al (2017) Molecular anatomy of the developing human retina. Dev Cell 43:763–779 e764
Izaddoost S, Nam SC, Bhat MA et al (2002) Drosophila Crumbs is a positional cue in photoreceptor adherens junctions and rhabdomeres. Nature 416:178–183
Jacobson SG, Cideciyan AV, Aleman TS et al (2003) Crumbs homolog 1 (CRB1) mutations result in a thick human retina with abnormal lamination. Hum Mol Genet 12:1073–1078
Kantardzhieva A, Gosens I, Alexeeva S et al (2005) MPP5 recruits MPP4 to the CRB1 complex in photoreceptors. Invest Ophthalmol Vis Sci 46:2192–2201
Kim JW, Yang HJ, Oel AP et al (2016) Recruitment of rod photoreceptors from short-wavelength-sensitive cones during the evolution of nocturnal vision in mammals. Dev Cell 37:520–532
Krol J, Krol I, Alvarez CP et al (2015) A network comprising short and long noncoding RNAs and RNA helicase controls mouse retina architecture. Nat Commun 6:7305
Letunic I, Bork P (2018) 20 years of the SMART protein domain annotation resource. Nucleic Acids Res 46:D493–D496
Luhmann UF, Carvalho LS, Holthaus SM et al (2015) The severity of retinal pathology in homozygous Crb1rd8/rd8 mice is dependent on additional genetic factors. Hum Mol Genet 24:128–141
Mattapallil MJ, Wawrousek EF, Chan CC et al (2012) The Rd8 mutation of the Crb1 gene is present in vendor lines of C57BL/6N mice and embryonic stem cells, and confounds ocular induced mutant phenotypes. Invest Ophthalmol Vis Sci 53:2921–2927
Mehalow AK, Kameya S, Smith RS et al (2003) CRB1 is essential for external limiting membrane integrity and photoreceptor morphogenesis in the mammalian retina. Hum Mol Genet 12:2179–2189
Pellikka M, Tanentzapf G, Pinto M et al (2002) Crumbs, the Drosophila homologue of human CRB1/RP12, is essential for photoreceptor morphogenesis. Nature 416:143–149
Pellissier LP, Lundvig DM, Tanimoto N et al (2014) CRB2 acts as a modifying factor of CRB1-related retinal dystrophies in mice. Hum Mol Genet 23:3759–3771
Quinn PM, Pellissier LP, Wijnholds J (2017) The CRB1 complex: following the trail of crumbs to a feasible gene therapy strategy. Front Neurosci 11:175
Sun Y, Vandenbriele C, Kauskot A et al (2015) A human platelet receptor protein microarray identifies the high affinity immunoglobulin E receptor subunit alpha (FcepsilonR1alpha) as an activating platelet endothelium aggregation receptor 1 (PEAR1) ligand. Mol Cell Proteomics 14:1265–1274
Talib M, van Schooneveld MJ, van Genderen MM et al (2017) Genotypic and phenotypic characteristics of CRB1-associated retinal dystrophies: a long-term follow-up study. Ophthalmology 124:884–895
Tisi D, Talts JF, Timpl R et al (2000) Structure of the C-terminal laminin G-like domain pair of the laminin alpha2 chain harbouring binding sites for alpha-dystroglycan and heparin. EMBO J 19:1432–1440
van de Pavert SA, Kantardzhieva A, Malysheva A et al (2004) Crumbs homologue 1 is required for maintenance of photoreceptor cell polarization and adhesion during light exposure. J Cell Sci 117:4169–4177
Vincent A, Ng J, Gerth-Kahlert C et al (2016) Biallelic mutations in CRB1 underlie autosomal recessive familial foveal retinoschisis. Invest Ophthalmol Vis Sci 57:2637–2646
Zhao S, Zhang B (2015) A comprehensive evaluation of ensembl, RefSeq, and UCSC annotations in the context of RNA-seq read mapping and gene quantification. BMC Genomics 16:97
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Ray, T.A., Cochran, K.J., Kay, J.N. (2019). The Enigma of CRB1 and CRB1 Retinopathies. 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_41
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DOI: https://doi.org/10.1007/978-3-030-27378-1_41
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