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

Rasmussen, Michel LU ; Welinder, Charlotte LU ; Schwede, Frank and Ekström, Per LU (2021) In Journal of Neurochemistry 157(6). p.2173-2186
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... (More)

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.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Chemical proteomics, Photoreceptors, Retinal degeneration, cGMP, cGMP-interacting proteins
in
Journal of Neurochemistry
volume
157
issue
6
pages
14 pages
publisher
Wiley-Blackwell
external identifiers
  • pmid:33230839
  • scopus:85097070898
ISSN
1471-4159
DOI
10.1111/jnc.15251
language
English
LU publication?
yes
additional info
This article is protected by copyright. All rights reserved.
id
14ac344a-6ea2-4983-997c-30ac821f6747
date added to LUP
2020-11-26 14:01:28
date last changed
2024-06-13 00:48:40
@article{14ac344a-6ea2-4983-997c-30ac821f6747,
  abstract     = {{<p>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.</p>}},
  author       = {{Rasmussen, Michel and Welinder, Charlotte and Schwede, Frank and Ekström, Per}},
  issn         = {{1471-4159}},
  keywords     = {{Chemical proteomics; Photoreceptors; Retinal degeneration; cGMP; cGMP-interacting proteins}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{6}},
  pages        = {{2173--2186}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of Neurochemistry}},
  title        = {{The cGMP system in normal and degenerating mouse neuroretina : New proteins with cGMP interaction potential identified by a proteomics approach}},
  url          = {{https://lup.lub.lu.se/search/files/90756456/The_cGMP_system_in_normal_and_degenerating_mouse_neuroretina_New_proteins_with_cGMP_interaction_potential_identified_by_a_proteomics_approach.pdf}},
  doi          = {{10.1111/jnc.15251}},
  volume       = {{157}},
  year         = {{2021}},
}