Phosphodiesterase 6H, cone-specific, gamma subunit (PDE6H)

Phosphodiesterase 6H is the inhibitory gamma subunit of the cone photoreceptor-specific cGMP phosphodiesterase complex (cone PDE6). It consists of 83 amino acids, tightly regulates the catalytic activity of PDE6 in the vertebrate retina, and is essential for daylight and color vision. In the dark, PDE6H maintains low cGMP hydrolysis by binding to cone PDE6’s catalytic dimer. Upon light activation, interaction with cone transducin relieves this inhibition, accelerating cGMP hydrolysis, closing cGMP-gated ion channels, and ultimately initiating hyperpolarization and visual signal transmission to the brain. Mutations or dysfunction in PDE6H are linked with achromatopsia and other cone-related vision disorders. Unlike the catalytic enzyme subunits, PDE6H alone does not have intrinsic catalytic activity nor is it a recognized drug target, but it is critical for the cone visual transduction pathway.

Other names

Cone Pγγ′ (gamma-prime)ACHM6GMP-PDE gammaRetinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gammaRCD3

Regulatory inhibition of cGMP hydrolysis by PDE6C in dark-adapted cones; Relief of inhibition upon light activation via interaction with transducin