Phosphodiesterase 6C, cGMP-specific cone alpha'


Phosphodiesterase 6C (PDE6C) is the catalytic subunit of the cone-specific photoreceptor phosphodiesterase, and serves as the central effector in the visual signaling pathway in vertebrate photoreceptor cells. The cone PDE6 holoenzyme consists of a catalytic dimer of two PDE6C subunits to which two molecules of the cone-specific inhibitory subunits (PDE6H) are bound. In the dark, cone PDE6 catalytic activity is low due to the binding of its inhibitory PDE6H subunit to the active site. Upon light activation of cone opsin (OPN1MW and OPN1SW) and the subsequent activation of cone-specific transducin α-subunit (GNAT2), cone PDE6 holoenzyme is activated by displacement of its inhibitory PDE6H subunit. Acceleration of cGMP hydrolysis ensues, causing closure of cGMP-gated ion channels and hyperpolarization of the cone outer segment membrane.

PDE6C, along with PDE6A and PDE6B (catalytic subunits for the rod PDE6 catalytic heterodimer), represent the photoreceptor-specific, cGMP phosphodiesterase family. All PDE6 isoforms strongly prefer cGMP over cAMP as the substrate, and catalyze cyclic nucleotide hydrolysis at a rate approaching the diffusion-controlled limit. PDE6 is one of eleven families that comprise the Class I phosphodiesterases. The PDE6 catalytic subunits consist of three distinct domains: a catalytic domain responsible for the hydrolysis of cyclic nucleotides, a GAFa domain to which cGMP binds in a noncatalytic manner, and a GAFb domain which links the GAFa and catalytic domains. The C-terminus of PDE6C is post-translationally modified by geranylgeranylation to permit attachment to the outer segment membrane.

Mutations in the PDE6C gene have been associated with several visual disturbances and retinal diseases, including achromatopsia and cone dystrophy.

Alternative names for this molecule: Pde6c; Phosphodiesterase 6C, cGMP specific, cone, alpha prime; Phosphodiesterase 6C, cGMP-specific cone alpha'

This molecule exists in 16 states, has 20 transitions between these states and has 7 enzyme functions. View high resolution network map

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UCSD Nature Molecule Pages


UCSD Signaling Gateway

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