{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T19:19:41Z","timestamp":1791055181047,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2006,12,13]],"date-time":"2006-12-13T00:00:00Z","timestamp":1165968000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2007,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cyclic nucleotide specific phosphodiesterases (PDEs) are pivotal regulators of cellular signaling. They are also important drug targets. Besides catalytic activity and substrate specificity, their subcel\u2010lular localization and interaction with other cell components are also functionally important. In contrast to the mammalian PDEs, the significance of PDEs in protozoal pathogens remains mostly unknown. The genome of\n                    <jats:italic>Trypanosoma brucei<\/jats:italic>\n                    , the causative agent of human sleeping sickness, codes for five different PDEs. Two of these, TbrPDEBl and TbrPDEB2, are closely similar, cAMP\u2010specific PDEs containing two GAF\u2010do\u2010mains in their N\u2010terminal regions. Despite their similarity, these two PDEs exhibit different subcellular localizations. TbrPDEB1 is located in the flagellum, whereas TbrPDEB2 is distributed between flagellum and cytoplasm. RNAi against the two mRNAs revealed that the two enzymes can complement each other but that a simultaneous ablation of both leads to cell death in bloodstream form trypanosomes. RNAi against Tbr\u2010PDEB1 and TbrPDEB2 also functions\n                    <jats:italic>in vivo<\/jats:italic>\n                    where it completely prevents infection and eliminates ongoing infections. Our data demonstrate that TbrPDEB1 and TbrPDEB2 are essential for virulence, making them valuable potential targets for new PDE\u2010inhibitor based trypanocidal drugs. Furthermore, they are compatible with the notion that the flagellum of\n                    <jats:italic>T. brucei<\/jats:italic>\n                    is an important site of cAMP signaling.\u2014Oberholzer, M., Marti, G., Baresic, M., Kunz, S., Hemphill, A., Seebeck, T. The\n                    <jats:italic>Trypanosoma brucei<\/jats:italic>\n                    cAMP phosphodiesterases TbrPDEB1 and TbrPDEB2: flagellar enzymes that are essential for parasite virulence.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    21, 720\u2013731 (2007)\n                  <\/jats:p>","DOI":"10.1096\/fj.06-6818com","type":"journal-article","created":{"date-parts":[[2006,12,13]],"date-time":"2006-12-13T21:56:53Z","timestamp":1166047013000},"page":"720-731","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":132,"title":["The\n                    <i>Trypanosoma brucei<\/i>\n                    cAMP phosphodiesterases TbrPDEBl and TbrPDEB2: flagellar enzymes that are essential for parasite virulence"],"prefix":"10.1096","volume":"21","author":[{"given":"Michael","family":"Oberholzer","sequence":"first","affiliation":[{"name":"Institute of Cell Biology University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Marti","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Baresic","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Kunz","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Hemphill","sequence":"additional","affiliation":[{"name":"Institute of Parasitology University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Seebeck","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,12,13]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0330257"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1085439"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1893"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000082524.34487.31"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/15216540400013861"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.21.5782"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.24.9303"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.12.019"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0061(200102)18:3<207::AID-YEA661>3.0.CO;2-I"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428190009057627"},{"key":"e_1_2_5_12_1","doi-asserted-by":"crossref","DOI":"10.1201\/9781420020847","volume-title":"Cyclic nucleotide phosphodiesterases in health and disease.","author":"Beavo J.","year":"2006"},{"key":"e_1_2_5_13_1","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/nature04468","article-title":"Structure of the cyclic\u2010AMP\u2010responsive exchange factor Epac2 in its auto\u2010inhibited state","volume":"439","author":"Rehman H.","year":"2006","journal-title":"Nature"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2005.05.014"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409917102"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M413611200"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000200178.34179.93"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0311186"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1074683"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000218493.09370.8e"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00021.2003"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1112915"},{"key":"e_1_2_5_23_1","first-page":"1998","article-title":"Impaired growth and fertility of cAMP\u2010specific phosphodiesterase PDE4D\u2010deficient mice","volume":"96","author":"Jin S. 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