Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 287, Issue 18, Pages 14873-14879Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M112.345751
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Funding
- National Institutes of Health [EY013811, MH094626, GM075033]
- NINDS/National Institutes of Health Center [5P30NS047463-02]
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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/G alpha(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 G beta 5S level is significantly reduced. By characterizing a complete RGS7 and RGS11 double knock-out (711dKO) mouse line, we found that G beta 5S expression in the retinal outer plexiform layer is eliminated, as is the ERGb-wave. Ultrastructural defects akin to those of G beta 5(-/-) mice are evident in 711dKO mice. In retinas of mice lacking RGS6, RGS7, and RGS11, G beta 5S is undetectable, whereas levels of the photoreceptor-specific G beta 5L remain unchanged. Whereas RGS6 alone sustains a significant amount of G beta 5S expression in retina, the DBC-related defects in G beta 5(-/-) mice are caused solely by a combined loss of RGS7 and RGS11. Our data support the notion that the role of G beta 5 in the retina, and likely in the entire nervous system, is mediated exclusively by R7 RGS proteins.
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