GAP-independent termination of photoreceptor light response by excess γ subunit of the cGMP-phosphodiesterase

SH Tsang, ML Woodruff, CK Chen… - Journal of …, 2006 - Soc Neuroscience
SH Tsang, ML Woodruff, CK Chen, CY Yamashita, MC Cilluffo, AL Rao, DB Farber, GL Fain
Journal of Neuroscience, 2006Soc Neuroscience
We have generated a mouse with rod photoreceptors overexpressing the γ inhibitory subunit
(PDE6γ) of the photoreceptor G-protein effector cGMP phosphodiesterase (PDE6). PDE6γ
overexpression decreases the rate of rise of the rod response at dim intensities, indicating a
reduction in the gain of transduction that may be the result of cytoplasmic PDE6γ binding to
activated transducin α GTP (Tα-GTP) before the Tα-GTP binds to endogenous PDE6γ.
Excess PDE6γ also produces a marked acceleration in the falling phase of the light …
We have generated a mouse with rod photoreceptors overexpressing the γ inhibitory subunit (PDE6γ) of the photoreceptor G-protein effector cGMP phosphodiesterase (PDE6). PDE6γ overexpression decreases the rate of rise of the rod response at dim intensities, indicating a reduction in the gain of transduction that may be the result of cytoplasmic PDE6γ binding to activated transducin α GTP (Tα-GTP) before the Tα-GTP binds to endogenous PDE6γ. Excess PDE6γ also produces a marked acceleration in the falling phase of the light response and more rapid recovery of sensitivity and circulating current after prolonged light exposure. These effects are not mediated by accelerating GTP hydrolysis through the GAP (GTPase activating protein) complex, because the decay of the light response is also accelerated in rods that overexpress PDE6γ but lack RGS9. Our results show that the PDE6γ binding sites of PDE6 α and β are accessible to excess (presumably cytoplasmic) PDE6γ in the light, once endogenous PDE6γ has been displaced from its binding site by Tα-GTP. They also suggest that in the presence of Tα-GTP, the PDE6γ remains attached to the rest of the PDE6 molecule, but after conversion of Tα-GTP to Tα-GDP, the PDE6γ may dissociate from the PDE6 and exchange with a cytoplasmic pool. This pool may exist even in wild-type rods and may explain the decay of rod photoresponses in the presence of nonhydrolyzable analogs of GTP.
Soc Neuroscience