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We identify a novel AC scaffold, the Popeye domain\u2010containing (POPDC) protein. The POPDC family of proteins is important for cardiac pacemaking and conduction, due in part to their cAMP\u2010dependent binding and regulation of TREK\u20101 potassium channels. We show that TREK\u20101 binds the AC9:POPDC1 complex and copurifies in a POPDC1\u2010dependent manner with AC9 activity in heart. Although the AC9:POPDC1 interaction is cAMP\u2010independent, TREK\u20101 association with AC9 and POPDC1 is reduced upon stimulation of the \u03b2\u2010adrenergic receptor (\u03b2AR). AC9 activity is required for \u03b2AR reduction of TREK\u20101 complex formation with AC9:POPDC1 and in reversing POPDC1 enhancement of TREK\u20101 currents. Finally, deletion of the gene\u2010encoding AC9 (\n                    <jats:italic>Adcy9)<\/jats:italic>\n                    gives rise to bradycardia at rest and stress\u2010induced heart rate variability, a milder phenotype than the loss of\n                    <jats:italic>Popdc1<\/jats:italic>\n                    but similar to the loss of\n                    <jats:italic>Kcnk2<\/jats:italic>\n                    (TREK\u20101). Thus, POPDC1 represents a novel adaptor for AC9 interactions with TREK\u20101 to regulate heart rate control.\n                  <\/jats:p>","DOI":"10.15252\/embr.202255208","type":"journal-article","created":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T06:52:09Z","timestamp":1666075929000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["POPDC1 scaffolds a complex of adenylyl cyclase 9 and the potassium channel TREK\u20101 in heart"],"prefix":"10.1038","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7142-639X","authenticated-orcid":false,"given":"Tanya A","family":"Baldwin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7440-6933","authenticated-orcid":false,"given":"Yong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Autumn N","family":"Marsden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2326-7069","authenticated-orcid":false,"given":"Susanne","family":"Rinn\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9011-0438","authenticated-orcid":false,"given":"Anibal","family":"Garza\u2010Carbajal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6823-9622","authenticated-orcid":false,"given":"Roland F R","family":"Schindler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Musi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mia A","family":"Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7977-4281","authenticated-orcid":false,"given":"Venugopal Reddy","family":"Venna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9433-687X","authenticated-orcid":false,"given":"Niels","family":"Decher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7090-5356","authenticated-orcid":false,"given":"Thomas","family":"Brand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1210-4280","authenticated-orcid":false,"given":"Carmen W","family":"Dessauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,10,18]]},"reference":[{"key":"BFEMBR202255208_CR1","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.bbi.2013.07.003","volume":"33","author":"S Acharjee","year":"2013","unstructured":"Acharjee S, Nayani N, Tsutsui M, Hill MN, Ousman SS, Pittman QJ (2013) Altered cognitive\u2010emotional behavior in early experimental autoimmune encephalitis\u2010\u2010cytokine and hormonal correlates. 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