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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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Gene Review: 

PDE9A  -  phosphodiesterase 9A

Homo sapiens

Synonyms: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A
 
 
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Disease relevance of PDE9A

  • The full-length PDE9A was expressed in baculovirus fused to an N-terminal 9-amino acid FLAG tag [1].
 

Psychiatry related information on PDE9A

  • Since functional disturbances in intraneuronal signal transmission via second messengers play an important role in the pathophysiology of affective disorders, PDE9A is a strong candidate for such a role by position and function [2].
 

High impact information on PDE9A

  • Polymorphisms in PDE9A and PDE11A were found to be associated with the diagnosis of MDD [3].
  • The kinetic properties of the PDE9A2 catalytic domain similar to those of full-length PDE9A imply that the N-terminal regulatory domain does not significantly alter the catalytic activity and the IBMX inhibition [4].
  • PDE9A lacks a region homologous to the allosteric cGMP-binding regulatory regions found in the cGMP-binding PDEs: PDE2, PDE5, and PDE6 [1].
  • The exon structure of PDE9A5 is different from those of PDEs 9A1, 9A2, 9A3 and 9A4 in that, of the 20 exons of PDE9A gene, it lacks exons 2 and 5 [5].
  • Identification and characterization of a new human type 9 cGMP-specific phosphodiesterase splice variant (PDE9A5). Differential tissue distribution and subcellular localization of PDE9A variants [5].
 

Biological context of PDE9A

  • PDE9A is insensitive (up to 100 microM) to a variety of PDE inhibitors including rolipram, vinpocetine, SKF-94120, dipyridamole, and 3-isobutyl-1-methyl-xanthine but is inhibited (IC50 = 35 microM) by zaprinast, a PDE5 inhibitor [1].
  • PDE9A is probably involved in maintenance of low cGMP levels in cells and might play an important role in a variety of brain functions involving cGMP-mediated signal transduction [6].
 

Anatomical context of PDE9A

  • PDE9A mRNA was widely distributed throughout the rat and mouse brain, with the highest expression observed in cerebellar Purkinje cells [6].
  • RESULTS: In the present study, we expressed different splice variants of PDE9A in HeLa and Cos-1 cells with EGFP fluorescent protein in phase with the catalytic domain sequence in order to test the different start codon usage in each splice variant [7].
 

Other interactions of PDE9A

 

Analytical, diagnostic and therapeutic context of PDE9A

  • In this study, we report the cloning of the rat cGMP-specific phosphodiesterase type 9 (PDE9A) and its localization in rat and mouse brain by non-radioactive in situ hybridization [6].
  • After treatment with soluble guanylyl cyclase activators the granular layer also showed cGMP staining, whereas no clear immunostaining was detected in Purkinje cells under all conditions investigated, which might be due to the presence of the IBMX-insensitive PDE9A in these cells [6].

References

  1. Isolation and characterization of PDE9A, a novel human cGMP-specific phosphodiesterase. Fisher, D.A., Smith, J.F., Pillar, J.S., St Denis, S.H., Cheng, J.B. J. Biol. Chem. (1998) [Pubmed]
  2. Identification and characterization of a novel cyclic nucleotide phosphodiesterase gene (PDE9A) that maps to 21q22.3: alternative splicing of mRNA transcripts, genomic structure and sequence. Guipponi, M., Scott, H.S., Kudoh, J., Kawasaki, K., Shibuya, K., Shintani, A., Asakawa, S., Chen, H., Lalioti, M.D., Rossier, C., Minoshima, S., Shimizu, N., Antonarakis, S.E. Hum. Genet. (1998) [Pubmed]
  3. Phosphodiesterase genes are associated with susceptibility to major depression and antidepressant treatment response. Wong, M.L., Whelan, F., Deloukas, P., Whittaker, P., Delgado, M., Cantor, R.M., McCann, S.M., Licinio, J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  4. Crystal structure of phosphodiesterase 9 shows orientation variation of inhibitor 3-isobutyl-1-methylxanthine binding. Huai, Q., Wang, H., Zhang, W., Colman, R.W., Robinson, H., Ke, H. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  5. Identification and characterization of a new human type 9 cGMP-specific phosphodiesterase splice variant (PDE9A5). Differential tissue distribution and subcellular localization of PDE9A variants. Wang, P., Wu, P., Egan, R.W., Billah, M.M. Gene (2003) [Pubmed]
  6. Cloning and localization of the cGMP-specific phosphodiesterase type 9 in the rat brain. van Staveren, W.C., Glick, J., Markerink-van Ittersum, M., Shimizu, M., Beavo, J.A., Steinbusch, H.W., de Vente, J. J. Neurocytol. (2002) [Pubmed]
  7. Specific use of start codons and cellular localization of splice variants of human phosphodiesterase 9A gene. Rentero, C., Puigdom??nech, P. BMC Mol. Biol. (2006) [Pubmed]
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