Publication Date:
2015-11-28
Description:
Publication date: Available online 26 November 2015 Source: FEBS Letters Author(s): Kyoung-in Cho, Victoria Hanley, Dosuk Yoon, Yin Hao, Paulo A. Ferreira 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 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-Ranbp2 CLDm with paradoxical age-dependent resistance of photoreceptors to death and genotype-independent caspase activation. Ranbp2 -/- ::Tg-Ranbp2 CLDm 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.
Print ISSN:
0014-5793
Electronic ISSN:
1873-3468
Topics:
Biology
,
Chemistry and Pharmacology
,
Physics
