Evidence for RPGRIP1 gene as risk factor for primary open angle glaucoma

Fernández-Martínez, Lorena T.; Letteboer, Stef J.F.; Mardin, Christian Y.; Weisschuh, Nicole; Gramer, E.; Weber, Bernhard H. F.; Rautenstrauß, Bernd; Ferreira, Paulo A.; Kruse, Friedrich E.; Reis, André; Roepman, Ronald; Pasutto, Francesca

doi:10.1038/ejhg.2010.217

Cited by 33 publications

(26 citation statements)

References 39 publications

(46 reference statements)

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“…By contrast, mutations in NPHP4 cause either familial juvenile nephronophthisis or the ocular-renal disease, Senior-Løken syndrome (SLSN) (Mollet et al, 2002; Otto et al, 2002). Further, heterozygous and LCA-distinct mutations outside the RID of RPGRIP1 were found recently to increase the susceptibility to or cause various forms of glaucoma (Fernandez-Martinez et al, 2011). Evidence also indicates that the components of the RPGRIP1 complex, PrBP/δ and RPGR, apparently associate or form high-order complexes with Rab13, Arl2, H-Ras, Rheb, Rho6, Rab8a, nephrocystin-5 (NPHP5) or CEP290/nephrocystin-6 (NPHP6) (Chang et al, 2006; Hanzal-Bayer et al, 2002; Murga-Zamalloa et al, 2010; Otto et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Structural and functional plasticity of subcellular tethering, targeting and processing of RPGRIP1 by RPGR isoforms

et al. 2011

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SummaryMutations affecting the retinitis pigmentosa GTPase regulator-interacting protein 1 (RPGRIP1) interactome cause syndromic retinal dystrophies. RPGRIP1 interacts with the retinitis pigmentosa GTPase regulator (RPGR) through a domain homologous to RCC1 (RHD), a nucleotide exchange factor of Ran GTPase. However, functional relationships between RPGR and RPGRIP1 and their subcellular roles are lacking. We show by molecular modeling and analyses of RPGR disease-mutations that the RPGR-interacting domain (RID) of RPGRIP1 embraces multivalently the shared RHD of RPGR1–19 and RPGRORF15 isoforms and the mutations are non-overlapping with the interface found between RCC1 and Ran GTPase. RPGR disease-mutations grouped into six classes based on their structural locations and differential impairment with RPGRIP1 interaction. RPGRIP1α1 expression alone causes its profuse self-aggregation, an effect suppressed by co-expression of either RPGR isoform before and after RPGRIP1α1 self-aggregation ensue. RPGR1–19 localizes to the endoplasmic reticulum, whereas RPGRORF15 presents cytosolic distribution and they determine uniquely the subcellular co-localization of RPGRIP1α1. Disease mutations in RPGR1–19, RPGRORF15, or RID of RPGRIP1α1, singly or in combination, exert distinct effects on the subcellular targeting, co-localization or tethering of RPGRIP1α1 with RPGR1–19 or RPGRORF15 in kidney, photoreceptor and hepatocyte cell lines. Additionally, RPGRORF15, but not RPGR1–19, protects the RID of RPGRIP1α1 from limited proteolysis. These studies define RPGR- and cell-type-dependent targeting pathways with structural and functional plasticity modulating the expression of mutations in RPGR and RPGRIP1. Further, RPGR isoforms distinctively determine the subcellular targeting of RPGRIP1α1, with deficits in RPGRORF15-dependent intracellular localization of RPGRIP1α1 contributing to pathomechanisms shared by etiologically distinct syndromic retinal dystrophies.

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Section: Introductionmentioning

confidence: 99%

Structural and functional plasticity of subcellular tethering, targeting and processing of RPGRIP1 by RPGR isoforms

et al. 2011

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“…Recently, a correlation between the RPGRIP1 gene and primary open-angle glaucoma was found, but this concerned mutations not associated with RP. 19 The unusual severe and rapidly blinding open-angle glaucoma seems to be a characteristic feature of WARD.…”

Section: Discussionmentioning

confidence: 99%

White Annular Retinal Dystrophy With Severe Glaucoma

Morizot

Schooneveld

Morizot³

2016

Retina

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“…In photoreceptors, the RPGRIP1 interactome was discovered to be comprised of at least three proteins, RGPRIP1 itself, RGPR and nephrocystin-4/nephroretinin (NPHP4) (Boylan and Wright 2000, Roepman, Schick et al 2000, Hong, Yue et al 2001, Roepman, Letteboer et al 2005). Mutations in RPGRIP1 have been associated with juvenile RP, Leber congenital amaurosis, cone-rod dystrophy as well as some forms of glaucoma (Dryja, Adams et al 2001, Gerber, Perrault et al 2001, Hameed, Abid et al 2003, Hanein, Perrault et al 2004, Booij, Florijn et al 2005, Galvin, Fishman et al 2005, Fernandez-Martinez, Letteboer et al 2011, Patil, Tserentsoodol et al 2012). …”

Section: Mutations Occurring In the Connecting Cilium (Transition mentioning

confidence: 99%

Aberrant protein trafficking in retinal degenerations: The initial phase of retinal remodeling

Bales

Gross

2016

Experimental Eye Research

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Retinal trafficking proteins are involved in molecular assemblies that govern protein transport, orchestrate cellular events involved in cilia formation, regulate signal transduction, autophagy and endocytic trafficking, all of which if not properly controlled initiate retinal degeneration. Improper function and or trafficking of these proteins and molecular networks they are involved in cause a detrimental cascade of neural retinal remodeling due to cell death, resulting as devastating blinding diseases. A universal finding in retinal degenerative diseases is the profound detection of retinal remodeling, occurring as a phased modification of neural retinal function and structure, which begins at the molecular level. Retinal remodeling instigated by aberrant trafficking of proteins encompasses many forms of retinal degenerations, such as the diverse forms of retinitis pigmentosa (RP) and disorders that resemble RP through mutations in the rhodopsin gene, retinal ciliopathies, and some forms of glaucoma and age-related macular degeneration (AMD). As a large majority of genes associated with these different retinopathies are overlapping, it is imperative to understand their underlying molecular mechanisms. This review will discuss some of the most recent discoveries in vertebrate retinal remodeling and retinal degenerations caused by protein mistrafficking.

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Evidence for RPGRIP1 gene as risk factor for primary open angle glaucoma

Cited by 33 publications

References 39 publications

Structural and functional plasticity of subcellular tethering, targeting and processing of RPGRIP1 by RPGR isoforms

Structural and functional plasticity of subcellular tethering, targeting and processing of RPGRIP1 by RPGR isoforms

White Annular Retinal Dystrophy With Severe Glaucoma

Aberrant protein trafficking in retinal degenerations: The initial phase of retinal remodeling

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