The cGMP system in normal and degenerating mouse neuroretina: New proteins with cGMP interaction potential identified by a proteomics approach

Michel Rasmussen, Charlotte Welinder, Frank Schwede, Per Ekström

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Abstract

The hereditary disease Retinitis pigmentosa results in severe vision loss due to photoreceptor degeneration by unclear mechanisms. In several disease models, the second messenger cGMP accumulates in the degenerating photoreceptors, where it may over-activate specific cGMP-interacting proteins, like cGMP-dependent protein kinase. Moreover, interventions that counteract the activity of these proteins lead to reduced photoreceptor cell death. Yet there is little or no information whether other than such regular cGMP-interactors are present in the retina, which we, therefore, investigated in wild-type and retinal degeneration (rd1, rd10, and rd2) mouse models. An affinity chromatography based proteomics approach that utilized immobilized cGMP analogs was applied to enrich and select for regular and potentially new cGMP-interacting proteins as identified by mass spectrometry. This approach revealed 12 regular and ten potentially new retinal cGMP-interacting proteins (e.g., EPAC2 and CaMKIIα). Several of the latter were found to be expressed in the photoreceptors and to have proximity to cGMP and may thus be of interest when defining prospective therapeutic targets or biomarkers for retinal degeneration.

Original languageEnglish
Pages (from-to)2173-2186
Number of pages14
JournalJournal of Neurochemistry
Volume157
Issue number6
Early online date2020 Nov 24
DOIs
Publication statusPublished - 2021 Jun 1

Bibliographical note

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Subject classification (UKÄ)

  • Biochemistry and Molecular Biology
  • Neurosciences

Free keywords

  • Chemical proteomics
  • Photoreceptors
  • Retinal degeneration
  • cGMP
  • cGMP-interacting proteins

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