TY - JOUR
T1 - Phosducin-like protein 1 is essential for G-protein assembly and signaling in retinal rod photoreceptors
AU - Lai, Chun Wan J.
AU - Kolesnikov, Alexander V.
AU - Frederick, Jeanne M.
AU - Blake, Devon R.
AU - Jiang, Li
AU - Stewart, Jubal S.
AU - Chen, Ching Kang
AU - Barrow, Jeffery R.
AU - Baehr, Wolfgang
AU - Kefalov, Vladimir J.
AU - Willardson, Barry M.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84877126346
U2 - 10.1523/JNEUROSCI.5001-12.2013
DO - 10.1523/JNEUROSCI.5001-12.2013
M3 - Article
C2 - 23637185
AN - SCOPUS:84877126346
SN - 0270-6474
VL - 33
SP - 7941
EP - 7951
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 18
ER -