June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Robust self-association of arrestin-1 is a neuroprotective mechanism
Author Affiliations & Notes
  • Eugenia Gurevich
    Pharmacology, Vanderbilt University, Nashville, TN
  • Xiufeng Song
    Pharmacology, Vanderbilt University, Nashville, TN
  • Jungwon Seo
    Pharmacology, Vanderbilt University, Nashville, TN
  • Faiza Baameur
    Pharmacology, Vanderbilt University, Nashville, TN
  • Sergey Vishnivetskiy
    Pharmacology, Vanderbilt University, Nashville, TN
  • Qiuyan Chen
    Pharmacology, Vanderbilt University, Nashville, TN
  • Miyeon Kim
    University of California Los Angeles, Los Angeles, CA
  • Jeannie Chen
    University of Southern California, Los Angeles, CA
  • Wayne Hubbell
    University of California Los Angeles, Los Angeles, CA
  • Vsevolod Gurevich
    Pharmacology, Vanderbilt University, Nashville, TN
  • Footnotes
    Commercial Relationships Eugenia Gurevich, None; Xiufeng Song, None; Jungwon Seo, None; Faiza Baameur, None; Sergey Vishnivetskiy, None; Qiuyan Chen, None; Miyeon Kim, None; Jeannie Chen, None; Wayne Hubbell, None; Vsevolod Gurevich, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 2456. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Eugenia Gurevich, Xiufeng Song, Jungwon Seo, Faiza Baameur, Sergey Vishnivetskiy, Qiuyan Chen, Miyeon Kim, Jeannie Chen, Wayne Hubbell, Vsevolod Gurevich; Robust self-association of arrestin-1 is a neuroprotective mechanism. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2456.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose: To determine the biological role of arrestin-1 self-association.

Methods: Retinal morphology and the health of rod photoreceptors in mice of different ages expressing wild type (WT) arrestin-1 and mutant with impaired self-association was compared.

Results: Arrestin-1 binds light-activated phosphorhodopsin and ensures timely signal shutoff. Arrestin-1 self-association is conserved in at least three mammalian species, but its biological role remains obscure. We found that high expression of arrestin-1 mutant with impaired oligomerization, but not of WT arrestin-1 that robustly oligomerizes, results in progressive rod degeneration via apoptosis. Synaptic terminals of rods are adversely affected earlier than other cell compartments. Dark rearing does not prevent mutant-induced cell death, ruling out the role of arrestin-rhodopsin complexes. WT arrestin-1 co-expressed with the mutant delays retinal degeneration, likely by forming mixed oligomers.

Conclusions: Monomeric arrestin-1 is cytotoxic, and it likely acquired propensity to oligomerize to reduce the concentration of the monomer in the cell. This finding suggests that cones express the bulk of their arrestin complement (~98%) in the form of arrestin-1 because cone-specific arrestin-4 is naturally oligomerization-deficient and therefore likely cytotoxic. The results also suggest that arrestin-1 binding to microtubules largely serves to minimize free monomer in the cell body, rather than to localize arrestin-1 away from the outer segment in the dark.

Keywords: 695 retinal degenerations: cell biology • 714 signal transduction • 740 transgenics/knock-outs  
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×