Uncoupling phototoxicity-elicited neural dysmorphology and death by insidious function and selective impairment of Ran-binding protein 2 (Ranbp2).

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Cho, K-I; Haney, V; Yoon, D; Hao, Y; Ferreira, PA

Published Date

  • December 21, 2015

Published In

Volume / Issue

  • 589 / 24 Pt B

Start / End Page

  • 3959 - 3968

PubMed ID

  • 26632511

Pubmed Central ID

  • 26632511

Electronic International Standard Serial Number (EISSN)

  • 1873-3468

Digital Object Identifier (DOI)

  • 10.1016/j.febslet.2015.11.037

Language

  • eng

Conference Location

  • England