Meta-Biol

• Pathways

Phosphodiesterase 6 (PDE6, Pittler et al. 1990, Tuteja et al. 1990, Weber et al. 1991) undergoes brief, spontaneous activations every few minutes to sustain a low, basal rate of 3',5' cyclic GMP (cGMP) hydrolysis to 5’ GMP (Cobbs 1991, Dawis et al. 1988, Hodgkin & Nunn 1988, Rieke & Baylor 1996, Wensel & Stryer 1986). However, activated transducin (GNAT1-GTP) sustains PDE6 activation allowing it to hydrolyze cGMP at a rate limited only by diffusional access to substrate (Chader et al. 1974, Goridis & Virmaux 1974, Miki et al. 1973). This event represents another amplification step in the phototransduction cascade wherein activated PDE6 hydrolyzes thousands of cGMP molecules per second. The decline in intracellular cGMP levels results in the closure of cyclic nucleotide gated cation channels (CNG channels). Mutations in the PDE6 subunits can cause retinitis pigmentosa or congenital stationary night blindness (https://sph.uth.edu/retnet/).