Retinal cone photoreceptors require phosducin-like protein 1 for G protein complex assembly and signaling.
G protein β subunits (Gβ) play essential roles in phototransduction as part of G protein βγ (Gβγ) and regulator of G protein signaling 9 (RGS9)-Gβ5 heterodimers. Both are obligate dimers that rely on the cytosolic chaperone CCT and its co-chaperone PhLP1 to form complexes from their nascent polypept...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4319785?pdf=render |
| _version_ | 1818477084372107264 |
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| author | Christopher M Tracy Alexander V Kolesnikov Devon R Blake Ching-Kang Chen Wolfgang Baehr Vladimir J Kefalov Barry M Willardson |
| author_facet | Christopher M Tracy Alexander V Kolesnikov Devon R Blake Ching-Kang Chen Wolfgang Baehr Vladimir J Kefalov Barry M Willardson |
| author_sort | Christopher M Tracy |
| collection | DOAJ |
| description | G protein β subunits (Gβ) play essential roles in phototransduction as part of G protein βγ (Gβγ) and regulator of G protein signaling 9 (RGS9)-Gβ5 heterodimers. Both are obligate dimers that rely on the cytosolic chaperone CCT and its co-chaperone PhLP1 to form complexes from their nascent polypeptides. The importance of PhLP1 in the assembly process was recently demonstrated in vivo in a retinal rod-specific deletion of the Phlp1 gene. To test whether this is a general mechanism that also applies to other cell types, we disrupted the Phlp1 gene specifically in mouse cones and measured the effects on G protein expression and cone visual signal transduction. In PhLP1-deficient cones, expression of cone transducin (Gt2) and RGS9-Gβ5 subunits was dramatically reduced, resulting in a 27-fold decrease in sensitivity and a 38-fold delay in cone photoresponse recovery. These results demonstrate the essential role of PhLP1 in cone G protein complex formation. Our findings reveal a common mechanism of Gβγ and RGS9-Gβ5 assembly in rods and cones, highlighting the importance of PhLP1 and CCT-mediated Gβ complex formation in G protein signaling. |
| first_indexed | 2024-12-10T09:33:37Z |
| format | Article |
| id | doaj.art-41dd7572ce18406d9175fa0dc4ac2c64 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T09:33:37Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-41dd7572ce18406d9175fa0dc4ac2c642022-12-22T01:54:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01102e011712910.1371/journal.pone.0117129Retinal cone photoreceptors require phosducin-like protein 1 for G protein complex assembly and signaling.Christopher M TracyAlexander V KolesnikovDevon R BlakeChing-Kang ChenWolfgang BaehrVladimir J KefalovBarry M WillardsonG protein β subunits (Gβ) play essential roles in phototransduction as part of G protein βγ (Gβγ) and regulator of G protein signaling 9 (RGS9)-Gβ5 heterodimers. Both are obligate dimers that rely on the cytosolic chaperone CCT and its co-chaperone PhLP1 to form complexes from their nascent polypeptides. The importance of PhLP1 in the assembly process was recently demonstrated in vivo in a retinal rod-specific deletion of the Phlp1 gene. To test whether this is a general mechanism that also applies to other cell types, we disrupted the Phlp1 gene specifically in mouse cones and measured the effects on G protein expression and cone visual signal transduction. In PhLP1-deficient cones, expression of cone transducin (Gt2) and RGS9-Gβ5 subunits was dramatically reduced, resulting in a 27-fold decrease in sensitivity and a 38-fold delay in cone photoresponse recovery. These results demonstrate the essential role of PhLP1 in cone G protein complex formation. Our findings reveal a common mechanism of Gβγ and RGS9-Gβ5 assembly in rods and cones, highlighting the importance of PhLP1 and CCT-mediated Gβ complex formation in G protein signaling.http://europepmc.org/articles/PMC4319785?pdf=render |
| spellingShingle | Christopher M Tracy Alexander V Kolesnikov Devon R Blake Ching-Kang Chen Wolfgang Baehr Vladimir J Kefalov Barry M Willardson Retinal cone photoreceptors require phosducin-like protein 1 for G protein complex assembly and signaling. PLoS ONE |
| title | Retinal cone photoreceptors require phosducin-like protein 1 for G protein complex assembly and signaling. |
| title_full | Retinal cone photoreceptors require phosducin-like protein 1 for G protein complex assembly and signaling. |
| title_fullStr | Retinal cone photoreceptors require phosducin-like protein 1 for G protein complex assembly and signaling. |
| title_full_unstemmed | Retinal cone photoreceptors require phosducin-like protein 1 for G protein complex assembly and signaling. |
| title_short | Retinal cone photoreceptors require phosducin-like protein 1 for G protein complex assembly and signaling. |
| title_sort | retinal cone photoreceptors require phosducin like protein 1 for g protein complex assembly and signaling |
| url | http://europepmc.org/articles/PMC4319785?pdf=render |
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