The membrane associated cGMP phosphodiesterase 6 (PDE6) is a tetramer of two catalytic chains, alpha (PDE6A or PDEA) (Pittler et al. 1990) and beta (PDE6B or PDEB) (Weber et al. 1991), and two inhibitory gamma chains (PDE6G or PDEG) (Tuteja et al. 1990). Binding of an activated transducin alpha subunit (GNAT1-GTP) to PDE-gamma relaxes the inhibitory effect of the gamma subunit thereby activating the associated alpha or beta catalytic subunit. Because the binding of GNAT1-GTP to PDE-gamma is one to one, there is no amplification associated with this step. Active Gt alpha (GNAT-GTP) can be inactivated by a slow, intrinsic GTPase activity that hydrolyses GTP to GDP. Once GNAT1 has GDP bound, it no longer binds to the gamma subunit of PDE6 (PDE6-gamma) that then resumes inhibition of the catalytic subunit of PDE6. Some forms of autosomal recessive retinitis pigmentosa and congenital stationary night blindness are caused by mutations in PDE6 (https://sph.uth.edu/retnet/).
Pittler, SJ, Baehr, W, Wasmuth, JJ, McConnell, DG, Champagne, MS, vanTuinen, P, Ledbetter, D, Davis, RL
Tuteja, N, Danciger, M, Klisak, I, Tuteja, R, Inana, G, Mohandas, T, Sparkes, RS, Farber, DB
Weber, B, Riess, O, Hutchinson, G, Collins, C, Lin, BY, Kowbel, D, Andrew, S, Schappert, K, Hayden, MR
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