PDE6A explained

Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha is an enzyme that in humans is encoded by the PDE6A gene.^{[1] [2] [3]}

PDE6A encodes the cyclic-GMP (cGMP) specific phosphodiesterase 6A alpha subunit, expressed in cells of the retinal rod outer segment. The phosphodiesterase 6 holoenzyme is a heterotrimer composed of an alpha, beta, and two gamma subunits. cGMP is an important regulator of rod cell membrane current, and its dynamic concentration is established by phosphodiesterase 6A cGMP hydrolysis and guanylate cyclase cGMP synthesis. Mutations in PDE6A have been identified as one cause of autosomal recessive retinitis pigmentosa.

Further reading

• Pittler SJ, Baehr W . The molecular genetics of retinal photoreceptor proteins involved in cGMP metabolism . Prog. Clin. Biol. Res. . 362 . 33–66 . 1991 . 1672236 .
• Takemoto DJ, Cunnick JM . Visual transduction in rod outer segments . Cell. Signal. . 2 . 2 . 99–104 . 1990 . 2169289 . 10.1016/0898-6568(90)90013-Z .
• Catty P, Pfister C, Bruckert F, Deterre P . The cGMP phosphodiesterase-transducin complex of retinal rods. Membrane binding and subunits interactions . J. Biol. Chem. . 267 . 27 . 19489–93 . 1992 . 10.1016/S0021-9258(18)41802-9 . 1326553 . free .
• Huang SH, Pittler SJ, Huang X, etal . Autosomal recessive retinitis pigmentosa caused by mutations in the alpha subunit of rod cGMP phosphodiesterase . Nat. Genet. . 11 . 4 . 468–71 . 1996 . 7493036 . 10.1038/ng1295-468 . 40530227 .
• Warrington JA, Bengtsson U . High-resolution physical mapping of human 5q31-q33 using three methods: radiation hybrid mapping, interphase fluorescence in situ hybridization, and pulsed-field gel electrophoresis . Genomics . 24 . 2 . 395–8 . 1995 . 7698768 . 10.1006/geno.1994.1636 .
• Mohamed MK, Taylor RE, Feinstein DS, etal . Structure and upstream region characterization of the human gene encoding rod photoreceptor cGMP phosphodiesterase alpha-subunit . J. Mol. Neurosci. . 10 . 3 . 235–50 . 1998 . 9770645 . 10.1007/BF02761777 . 27495644 .
• Mou H, Grazio HJ, Cook TA, etal . cGMP binding to noncatalytic sites on mammalian rod photoreceptor phosphodiesterase is regulated by binding of its gamma and delta subunits . J. Biol. Chem. . 274 . 26 . 18813–20 . 1999 . 10373499 . 10.1074/jbc.274.26.18813 . free .
• Dryja TP, Rucinski DE, Chen SH, Berson EL . Frequency of mutations in the gene encoding the alpha subunit of rod cGMP-phosphodiesterase in autosomal recessive retinitis pigmentosa . Invest. Ophthalmol. Vis. Sci. . 40 . 8 . 1859–65 . 1999 . 10393062 .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Pittler SJ, Zhang Y, Chen S, etal . Functional analysis of the rod photoreceptor cGMP phosphodiesterase alpha-subunit gene promoter: Nrl and Crx are required for full transcriptional activity . J. Biol. Chem. . 279 . 19 . 19800–7 . 2004 . 15001570 . 10.1074/jbc.M401864200 . free .
• Riazuddin SA, Zulfiqar F, Zhang Q, etal . Mutations in the gene encoding the alpha-subunit of rod phosphodiesterase in consanguineous Pakistani families . Mol. Vis. . 12 . 1283–91 . 2006 . 17110911 .

External links

• GeneReviews/NCBI/NIH/UW entry on Retinitis Pigmentosa Overview

Notes and References

1. Pittler SJ, Baehr W, Wasmuth JJ, McConnell DG, Champagne MS, vanTuinen P, Ledbetter D, Davis RL . Molecular characterization of human and bovine rod photoreceptor cGMP phosphodiesterase alpha-subunit and chromosomal localization of the human gene . Genomics . 6 . 2 . 272–83 . Apr 1990 . 2155175 . 10.1016/0888-7543(90)90567-E .
2. Web site: Entrez Gene: PDE6A phosphodiesterase 6A, cGMP-specific, rod, alpha.
3. Gulati S, Palczewski K, Engel A, Stahlberg H, Kovacik L . Cryo-EM structure of phosphodiesterase 6 reveals insights into the allosteric regulation of type I phosphodiesterases . Science Advances . 27 . 5 . Feb 2019 . eaav4322 . 30820458 . 10.1126/sciadv.aav4322 . 6392808 . 2019SciA....5.4322G .