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