Defective retinal depolarizing bipolar cells in regulators of G protein signaling (RGS) 7 and 11 double null mice

Hoon Shim; Chih-Ting Wang; Yen-Lin Chen; Viet Q Chau; Kevin G Fu; Jianqi Yang; A Rory McQuiston; Rory A Fisher; Ching-Kang Chen

doi:10.1074/jbc.M112.345751

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Defective retinal depolarizing bipolar cells in regulators of G protein signaling (RGS) 7 and 11 double null mice

Journal article

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Defective retinal depolarizing bipolar cells in regulators of G protein signaling (RGS) 7 and 11 double null mice

Hoon Shim, Chih-Ting Wang, Yen-Lin Chen, Viet Q Chau, Kevin G Fu, Jianqi Yang, A Rory McQuiston, Rory A Fisher and Ching-Kang Chen

The Journal of biological chemistry, Vol.287(18), pp.14873-14879

04/27/2012

DOI: 10.1074/jbc.M112.345751

PMCID: PMC3340290

PMID: 22371490

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Abstract

Two members of the R7 subfamily of regulators of G protein signaling, RGS7 and RGS11, are present at dendritic tips of retinal depolarizing bipolar cells (DBCs). Their involvement in the mGluR6/Gα(o)/TRPM1 pathway that mediates DBC light responses has been implicated. However, previous genetic studies employed an RGS7 mutant mouse that is hypomorphic, and hence the exact role of RGS7 in DBCs remains unclear. We have made a true RGS7-null mouse line with exons 6-8 deleted. The RGS7(-/-) mouse is viable and fertile but smaller in body size. Electroretinogram (ERG) b-wave implicit time in young RGS7(-/-) mice is prolonged at eye opening, but the phenotype disappears at 2 months of age. Expression levels of RGS6 and RGS11 are unchanged in RGS7(-/-) retina, but the Gβ5S level is significantly reduced. By characterizing a complete RGS7 and RGS11 double knock-out (711dKO) mouse line, we found that Gβ5S expression in the retinal outer plexiform layer is eliminated, as is the ERG b-wave. Ultrastructural defects akin to those of Gβ5(-/-) mice are evident in 711dKO mice. In retinas of mice lacking RGS6, RGS7, and RGS11, Gβ5S is undetectable, whereas levels of the photoreceptor-specific Gβ5L remain unchanged. Whereas RGS6 alone sustains a significant amount of Gβ5S expression in retina, the DBC-related defects in Gβ5(-/-) mice are caused solely by a combined loss of RGS7 and RGS11. Our data support the notion that the role of Gβ5 in the retina, and likely in the entire nervous system, is mediated exclusively by R7 RGS proteins.

RGS Proteins - genetics

Retina - metabolism

Animals

Gene Expression Regulation - genetics

RGS Proteins - metabolism

GTP-Binding Protein beta Subunits - biosynthesis

Mice

Retina - pathology

GTP-Binding Protein beta Subunits - genetics

Mice, Knockout

Details

Title: Subtitle: Defective retinal depolarizing bipolar cells in regulators of G protein signaling (RGS) 7 and 11 double null mice
Creators: Hoon Shim - Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298, USA
Chih-Ting Wang
Yen-Lin Chen - Virginia Commonwealth University
Viet Q Chau
Kevin G Fu
Jianqi Yang
A Rory McQuiston
Rory A Fisher
Ching-Kang Chen
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.287(18), pp.14873-14879
DOI: 10.1074/jbc.M112.345751
PMID: 22371490
PMCID: PMC3340290
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: GM075033 / NIGMS NIH HHS EY013811 / NEI NIH HHS 5P30NS047463-02 / NINDS NIH HHS MH094626 / NIMH NIH HHS P30 NS047463 / NINDS NIH HHS R01 GM075033 / NIGMS NIH HHS R01 MH094626 / NIMH NIH HHS R01 EY013811 / NEI NIH HHS R56 EY013811 / NEI NIH HHS
Language: English
Date published: 04/27/2012
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040252502771

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