Overview of PDE isoform localization
| Isoform | Localization | |
|---|---|---|
| Tissue/Cellular | Intracellular | |
| PDE1A | Smooth muscle, heart, lung, brain, sperm; PDE1A1 in lung and heart, PDE1A2 in brain | Predominantly cytosolic |
| PDE1B | PDE1B1 in neurons, lymphocytes, and smooth muscle; PDE1B2 in macrophages and lymphocytes | Cytosolic |
| PDE1C | Brain, proliferating human smooth muscle, spermatids; PDE1C2 in olfactory epithelium | Cytosolic |
| PDE2A | Adrenal medulla, brain, heart, platelet, macrophage subsets, endothelial cell subsets; PDE2 is highly localized to unique neuronal populations and brain regions | PDE2A3 and PDE2A2 variants are membrane-bound, whereas PDE2A1 is cytosolic |
| PDE3A | Heart, vascular smooth muscle, platelets, oocyte, kidney; PDE3A variants have differential expression in cardiovascular tissues | Can be either membrane-associated or cytosolic, depending on the variant and the cell type it is expressed in |
| PDE3B | Vascular smooth muscle, adipocytes, hepatocytes, kidney, β cells, developing sperm, T lymphocytes, macrophages | Predominantly membrane-associated; Localized to endoplasmic reticulum and microsomal fractions |
| PDE4A | Widely expressed with mRNA found in many tissues; olfactory system, immune cells, and testis; high levels of several of the variants are distributed throughout the brain | PDE4A5 is localized to membrane ruffles through its Src homology domain; the supershort variant PDE4A1 is entirely membrane-associated; PDE4A4 associates with Src family kinases; PDE4A5 is localized by AKAP binding; PDE4s can be recruited to interact with β -arrestin; PDE4A is recruited to a lipid raft fraction in activated T cells |
| PDE4B | High levels of mRNA detected in a variety of tissues; notable expression in immune cells and the brain | PDE4s can be recruited to interact with β -arrestin; is recruited to a lipid raft fraction in activated T cells |
| PDE4C | More restricted expression compared with other PDE4 isoforms; mRNA found in lung, testis, and several cell lines mainly of neuronal origin | Predominantly cytosolic; PDE4s can be recruited to interact with β -arrestin |
| PDE4D | mRNA widely distributed and found in a variety of tissues; protein levels high in the brain and in several other tissues as well; expression of variants seems to be localized to specific tissues and regions; variants are found in many commonly used cell lines (HEK293, COS) and in inflammatory cells | Depending on the identity of the variant, can be found in cytosolic or particulate fractions; PDE4D3 is localized by binding to mAKAP and AKAP450; PDE4D3 is a part of the cardiac RyR2 channel complex; PDE4D5 interacts with RACK1; can be recruited to interact with β -arrestin; is recruited to a lipid raft fraction in activated T cells |
| PDE5A | Platelets, vascular smooth muscle, brain, lung, heart, kidney, skeletal muscle; PDE5A1 and PDE5A2 are widely expressed, whereas PDE5A3 is specific to vascular smooth muscle | Cytosolic |
| PDE6A/PDE6B | High expression in rod cells of the photoreceptor layer of retina; also found in pineal gland | Targeted to the membrane by isoprenylation; association with the δ subunit results in cytosolic localization |
| PDE6C | High expression in cone cells of the photoreceptor layer of retina; also found in pineal gland | Cytosolic by virtue of its association with the δ subunit |
| PDE7A | Immune cells, heart, skeletal muscle, endothelial cells; PDE7A1 protein detected in a variety of immune cells, whereas PDE7A2 protein was found only in cardiac tissue | Cytosolic; localizes with AKAP MTG in lymphocytes |
| PDE7B | mRNA found in brain, heart, liver, skeletal muscle, pancreas, testis; in rat, PDE7B3 expression was restricted to the heart, whereas PDE7B2 was only found in testis; PDE7B1 is expressed in multiple tissues | Cytosolic |
| PDE8A | mRNA found in many tissues but highest in testis, spleen, small intestine, ovary, colon, and kidney; PDE8A2-5 is expressed in much lower abundance than PDE8A1; differential localization of PDE8A1 and PDE8A2 mRNA | Found in both cytosolic and particulate fractions |
| PDE8B | Brain and thyroid; variant expression is differential as PDE8B1 is expressed only in thyroid, whereas PDE8B3 is expressed equally in brain and thyroid | Found in both cytosolic and particulate fractions |
| PDE9A | mRNA for most variants has been detected in nearly every tissue tested with highest levels in kidney, brain, spleen, various gastrointestinal tissues, and prostate; variants expressed differentially | PDE9A5 protein has been shown to be cytosolic, whereas PDE9A1 is localized to the nucleus |
| PDE10A | Highest expression in brain, testis, heart, and thyroid; also reported in pituitary gland and in striated and cardiac muscle; PDE10A2 mRNA expression seems to be higher than that for PDE10A1 in most tissues | PDE10A1 and PDE10A3 variants are cytosolic, whereas PDE10A2 is particulate; PDE10A2 phosphorylation triggers translocation of the enzyme from the Golgi to the cytosol |
| PDE11A | mRNA found in skeletal muscle, prostate, testis, salivary gland, thyroid gland, and liver; PDE11A1 is most prominent in skeletal muscle; PDE11A3 is specific to testis; PDE11A4 is highest in prostate | Cytosolic |