Retinal G-substrate, potential downstream component of NO/cGMP/PKG pathway, is located in subtype of retinal ganglion cells and amacrine cells with protein phosphatases

Toru Nakazawa, Shogo Endo, Masahiko Shimura, Mineo Kondo, Shinji Ueno, Makoto Tamai

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

The aim of this study was to determine the distribution and function of G-substrate, a specific substrate of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-cGMP-dependent protein kinase (PKG) signaling pathway, in normal rat retina and in G-substrate knockout mice. The retinas of adult wild-type rats and mice and G-substrate knockout mice were studied immunohistologically to characterize the upstream and downstream components of the NO-cGMP-PKG pathway. Immunoblot analysis showed that the molecular weight of retinal G-substrate was similar to that of cerebellar G-substrate. In adult rats and mice, retinal G-substrate was located in a subpopulation of amacrine cells and in C38-positive retinal ganglion cells (RGCs) but not in alpha RGCs. In addition, retinal G-substrate was co-expressed with other upstream and downstream signaling components of the NO-cGMP-PKG-G-substrate-phosphatase pathway in the adult retina. Electroretinographic (ERG) analysis demonstrated that there was no significant difference between the ERGs of wild-type and G-substrate knockout mice. These results suggest that retinal G-substrate plays a role as a downstream component of the NO-cGMP-PKG pathway. The co-localization of retinal G-substrate with protein Ser/Thr phosphatases suggests that it acts as an endogenous protein phosphatase inhibitor as in the cerebellum.

Original languageEnglish
Pages (from-to)58-68
Number of pages11
JournalMolecular Brain Research
Volume135
Issue number1-2
DOIs
Publication statusPublished - 2005 Apr 27

Keywords

  • Cyclic GMP
  • Excitatory amino acids
  • Nitric oxide
  • Protein kinase
  • Signal transduction

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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