期刊
JOURNAL OF NEUROCHEMISTRY
卷 157, 期 6, 页码 2173-2186出版社
WILEY
DOI: 10.1111/jnc.15251
关键词
cGMP; cGMP-interacting proteins; Chemical proteomics; Photoreceptors; Retinal degeneration
资金
- Ogonfonden
- European Union (transMed) [MSCA-ITN-2017-765441]
- Stiftelsen Kronprinsessan Margaretas Arbetsnamnd for Synskadade
- Stiftelsen for Synskadade i f.d. Malmohus lan
Studies have identified various cGMP-interacting proteins in the retina, which may help reduce photoreceptor cell death and serve as potential therapeutic targets or biomarkers for retinal degeneration.
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 10 potentially new retinal cGMP-interacting proteins (e.g., EPAC2 and CaMKII alpha). 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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