Uncoupling phototoxicity-elicited neural dysmorphology and death by insidious function and selective impairment of Ran-binding protein 2 (Ranbp2).
Uncoupling phototoxicity-elicited neural dysmorphology and death by insidious function and selective impairment of Ran-binding protein 2 (Ranbp2).
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DOI：
10.1016/j.febslet.2015.11.037
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发表时间：
2015-12-21
期刊：
影响因子：
3.5
通讯作者：
Ferreira PA
中科院分区：
文献类型：
--
作者：
Cho KI;Haney V;Yoon D;Hao Y;Ferreira PA
神经元的形态学解体总是伴随着神经元的死亡。特别是，破坏感光神经元的外节触发感光细胞死亡，无论病理应激。我们发现，Ranbp 2 −/−：：Tg-Ranbp 2CLDm小鼠在无Ranbp 2背景下表达的Ranbp 2的亲环蛋白样结构域（CLD）的SUMO结合基序（SBM）突变，在光应激的情况下对光感受器没有不良影响。然而，与野生型光感受器相比，光应激导致Ranbp 2 −/−：：Tg-Ranbp 2CLDm外节的深刻解体，光感受器对死亡和基因型无关的caspase激活具有自相矛盾的年龄依赖性抗性。Ranbp 2 −/−：：Tg-Ranbp 2CLDm在泛素-蛋白酶体系统（UPS）中表现出光感受器死亡非依赖性变化，但死亡依赖性增加ubc 9水平。因此，Ranbp 2的CLD的SBM的潜在功能损害促进神经保护以及光感受器变性和死亡对抗光毒性的解偶联。
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-Ranbp2CLDm mice with mutations in SUMO-binding motif (SBM) of cyclophilin-like domain (CLD) of 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-Ranbp2CLDm with paradoxical age-dependent resistance of photoreceptors to death and genotype-independent caspase activation. Ranbp2−/−::Tg-Ranbp2CLDm exhibit photoreceptor death-independent changes in ubiquitin-proteasome system (UPS), but death-dependent increase of ubc9 levels. Hence, insidious functional impairment of SBM of Ranbp2’s CLD promotes neuroprotection and uncoupling of photoreceptor degeneration and death against phototoxicity.