%0 Journal Article
%T Specific use of start codons and cellular localization of splice variants of human phosphodiesterase 9A gene
%A Carles Rentero
%A Pere Puigdom¨¨nech
%J BMC Molecular Biology
%D 2006
%I BioMed Central
%R 10.1186/1471-2199-7-39
%X 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. It was found that at least two ATG start codons may be used and that the open reading frame that includes the catalytic domain may be translated. In addition the proteins produced from some of the splice variants are targeted to membrane ruffles and cellular vesicles while other variants appear to be cytoplasmic. A hypothesis about the functional meaning of these results is discussed.Our data suggest the utilization of two different start codons to produce a variety of different PDE9A proteins, allowing specific subcellular location of PDE9A splice variants.Cyclic nucleotide monophosphates (cAMP and cGMP) are ubiquitous second intracellular messengers which play an essential role in the transduction of a variety of extracellular signals. The control of intracellular cyclic nucleotide levels is achieved by different enzymes, including cyclases that synthesize the cyclic nucleotides and catabolic enzymes such as cyclic nucleotide phosphodiesterases (PDEs). At least twenty one genes coding for cyclic nucleotide PDEs have been identified in mammals. They have been classified in 11 families and in humans they code for more than 60 different isoforms through alternative splicing [1-3].The PDE9A gene encodes a cGMP-specific high-affinity PDE with widespread expression in most of the tissues examined [4-6]. The human PDE9A gene is located on 21q22.3, and has at least 22 exons spanning 122 kb. Because of its mapping position PDE9A is a possible candidate for genetic diseases mapped on 21q22.3, such as bipolar affective disorder. Furthermore, its overexpression might be involved in Down's syndrome [5]. For these reasons the expression in brain tissues of PDE9A, and also other PDEs, has been studied [7-9]. BAY 73¨C6691, a potent and selectiv
%U http://www.biomedcentral.com/1471-2199/7/39