The second messengers cAMP and cGMP are key regulatory molecules that are involved in a wide variety of signal transduction pathways, such as insulin secretion, platelet aggregation, smooth muscle relaxation, olfaction, and vision. Levels of cAMP and cGMP are regulated by their rate of synthesis by nucleotide cyclases and by their rate of hydrolysis by cyclic nucleotide phosphodiesterases (PDEs). PDEs form a superfamily of enzymes that catalyze the conversion of 3-prime, 5-prime-cyclic nucleotides to the corresponding nucleoside 5-prime-monophosphates. While mammalian PDEs are divided into major families based on their substrate specificities, kinetic properties, allosteric regulators, inhibitor sensitivities, and amino acid sequences, each family and even members within a family display distinct tissue, cell, and subcellular expression patters. This suggests that individual PDE family members are involved in discrete signal transduction pathways.
PDE6 is the effector enzyme in the G protein-mediated signal transduction cascade in the visual system. There are five different subunits consisting of rod and cone specific catalytic subunits: alpha’ (Cone), alpha (Rod), and beta (Rod), the inhibitory subunit gamma, and subunit delta of unknown function (which likely interacts with many other proteins besides the PDE6 family). The catalytic core of the PDE6 system is comprised of alpha’/alpha’ homodimers in the cone and alpha/beta heterodimers in the rod. The C-terminus of both the catalytic and inhibitory subunits is modified by methylation, myristyolation and prenylation which have been shown to be critical for proper complex assembly and membrane association.
Participates in processes of transmission and amplification of the visual signal. cGMP-PDEs are the effector molecules in G-protein-mediated phototransduction in vertebrate rods and cones.
Involvement in disease
Defects in PDE6G are the cause of retinitis pigmentosa type 57 (RP57) [MIM:613582]. RP57 is a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.
Belongs to the rod/cone cGMP-PDE gamma subunit family.