Photoreceptor phosphodiesterase (PDE6): activation and inactivation mechanisms during visual transduction in rods and cones
| Autor: | Rick H. Cote |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
genetic structures Physiology Clinical Biochemistry Context (language use) Protein Structure Secondary Article 03 medical and health sciences 0302 clinical medicine Retinal Rod Photoreceptor Cells Physiology (medical) Heterotrimeric G protein medicine Animals Humans Vision Ocular Retina Cyclic Nucleotide Phosphodiesterases Type 6 Chemistry Phosphodiesterase Photoreceptor outer segment Cell biology Protein Structure Tertiary 030104 developmental biology medicine.anatomical_structure Retinal Cone Photoreceptor Cells sense organs Transducin Signal transduction 030217 neurology & neurosurgery Visual phototransduction |
| Zdroj: | Pflugers Arch |
| ISSN: | 1432-2013 |
| Popis: | Rod and cone photoreceptors of the vertebrate retina utilize cGMP as the primary intracellular messenger for the visual signaling pathway that converts a light stimulus into an electrical response. cGMP metabolism in the signal-transducing photoreceptor outer segment reflects the balance of cGMP synthesis (catalyzed by guanylyl cyclase) and degradation (catalyzed by the photoreceptor phosphodiesterase, PDE6). Upon light stimulation, rapid activation of PDE6 by the heterotrimeric G-protein (transducin) triggers a dramatic drop in cGMP levels that lead to cell hyperpolarization. Following cessation of the light stimulus, the lifetime of activated PDE6 is also precisely regulated by additional processes. This review summarizes recent advances in the structural characterization of the rod and cone PDE6 catalytic and regulatory subunits in the context of previous biochemical studies of the enzymological properties and allosteric regulation of PDE6. Emphasis is given to recent advances in understanding the structural and conformational changes underlying the mechanism by which the activated transducin α-subunit binds to—and relieves inhibition of—PDE6 catalysis that is controlled by its intrinsically disordered, inhibitory γ-subunit. The role of the regulator of G-protein signaling 9–1 (RGS9-1) in regulating the lifetime of the transducin-PDE6 is also briefly covered. The therapeutic potential of pharmacological compounds acting as inhibitors or activators targeting PDE6 is discussed in the context of inherited retinal diseases resulting from mutations in rod and cone PDE6 genes as well as other inherited defects that arise from excessive cGMP accumulation in retinal photoreceptor cells. |
| Databáze: | OpenAIRE |
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