title: Uncoupling phototoxicity-elicited neural dysmorphology and death by insidious function and selective impairment of Ran-binding protein 2 (Ranbp2).
abstract: Morphological disintegration of neurons is coupled invariably to neural death. In particular, disruption of outer segments of photoreceptor neurons triggers photoreceptor death regardless of the pathological stressors. We show that Ranbp2(-/-)::Tg-Ranbp2(CLDm-HA) mice with mutations in SUMO-binding motif (SBM) of cyclophilin-like domain (CLD) of Ran-binding protein 2 (Ranbp2) expressed in a null Ranbp2 background lack untoward effects in photoreceptors in the absence of light-stress. However, compared to wild type photoreceptors, light-stress elicits profound disintegration of outer segments of Ranbp2(-/-)::Tg-Ranbp2(CLDm-HA) with paradoxical age-dependent resistance of photoreceptors to death and genotype-independent activation of caspases. Ranbp2(-/-)::Tg-Ranbp2(CLDm-HA) exhibit photoreceptor death-independent changes in ubiquitin-proteasome system (UPS), but death-dependent increase of ubiquitin carrier protein 9(ubc9) levels. Hence, insidious functional impairment of SBM of Ranbp2's CLD promotes neuroprotection and uncoupling of photoreceptor degeneration and death against phototoxicity.
authors.affiliation: Department of Ophthalmology, Duke University Medical Center, Durham, NC 27710, United States.
authors.forename: Kyoung-in
authors.initials: KI
authors.lastname: Cho
authors.affiliation: Department of Ophthalmology, Duke University Medical Center, Durham, NC 27710, United States.
authors.forename: Victoria
authors.initials: V
authors.lastname: Haney
authors.affiliation: Department of Ophthalmology, Duke University Medical Center, Durham, NC 27710, United States.
authors.forename: Dosuk
authors.initials: D
authors.lastname: Yoon
authors.affiliation: Department of Ophthalmology, Duke University Medical Center, Durham, NC 27710, United States.
authors.forename: Yin
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Department of Ophthalmology, Duke University Medical Center, Durham, NC 27710, United States; Department of Pathology, Duke University Medical Center, Durham, NC 27710, United States. Electronic address: paulo.ferreira@duke.edu.
authors.forename: Paulo A
authors.initials: PA
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D003433:Crosses, Genetic; D015536:Down-Regulation; D004789:Enzyme Activation / Q000528:radiation effects; D008027:Light / Q000009:adverse effects*; D018345:Mice, Knockout; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism* / Q000528:radiation effects / Q000648:ultrastructure; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism / Q000528:radiation effects / Q000648:ultrastructure; D054730:Protein Interaction Domains and Motifs; D059748:Proteolysis / Q000528:radiation effects; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D028861:Nuclear Pore Complex Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C094493:ran-binding protein 2; D044763:Ubiquitin-Conjugating Enzymes; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053181:Caspase 8; D053453:Caspase 9; D046988:Proteasome Endopeptidase Complex; D000098843:Ubiquitin-Conjugating Enzyme UBC9
keywords: Cyclophilin-like domain; Neuroprotection; Photoreceptor neuron; Phototoxicity; Ran-binding protein 2; SUMOylation