Abstract
G-protein β subunits perform essential neuronal functions as part of G-protein βγ and Gβ5-regulators of G-protein signaling (RGS) complexes. Both Gβγ and Gβ5-RGS are obligate dimers that are thought to require the assistance of the cytosolic chaperonin CCT and a cochaperone, phosducin-like protein 1 (PhLP1) for dimer formation. To test this hypothesis in vivo, we deleted the Phlp1 gene in mouse (Mus musculus) retinal rod photoreceptor cells and measured the effects on G-protein biogenesis and visual signal transduction. In the PhLP1-depleted rods, Gβγ dimer formation was decreased 50-fold, resulting in a >10-fold decrease in light sensitivity. Moreover, a 20-fold reduction in Gβ5 and RGS9-1 expression was also observed, causing a 15-fold delay in the shutoff of light responses. These findings conclusively demonstrate in vivo that PhLP1 is required for the folding and assembly of both Gβγ and Gβ5-RGS9.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biophysical Phenomena / genetics
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Contrast Sensitivity / genetics
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Dose-Response Relationship, Radiation
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Electric Stimulation
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Electroretinography
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Eye Proteins / genetics
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Eye Proteins / metabolism*
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GTP-Binding Protein beta Subunits / metabolism
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GTP-Binding Protein gamma Subunits / metabolism
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GTP-Binding Proteins / metabolism*
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Gene Expression Regulation / genetics
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In Vitro Techniques
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Light
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Membrane Potentials / genetics
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Membrane Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Patch-Clamp Techniques
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Photic Stimulation
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RNA, Messenger / metabolism
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Retina / cytology*
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Retinal Degeneration / genetics
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Retinal Degeneration / pathology
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Retinal Degeneration / physiopathology
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Retinal Rod Photoreceptor Cells / metabolism*
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Signal Transduction / physiology*
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Visual Acuity / genetics
Substances
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Eye Proteins
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G-protein Beta gamma
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GTP-Binding Protein beta Subunits
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GTP-Binding Protein gamma Subunits
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Membrane Proteins
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R9AP protein, mouse
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RNA, Messenger
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phosducin-like orphan protein-1
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GTP-Binding Proteins