{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:40:33Z","timestamp":1790642433587,"version":"4.1.0"},"reference-count":67,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL133256"],"award-info":[{"award-number":["HL133256"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL137745"],"award-info":[{"award-number":["HL137745"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL155180"],"award-info":[{"award-number":["HL155180"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["Hl155186"],"award-info":[{"award-number":["Hl155186"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL19134"],"award-info":[{"award-number":["HL19134"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["20POST35210200"],"award-info":[{"award-number":["20POST35210200"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["855946"],"award-info":[{"award-number":["855946"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL149662"],"award-info":[{"award-number":["HL149662"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2022,2,25]]},"abstract":"<jats:p>\n                    Polycystin-1 (PC-1, PKD1), a receptor-like protein expressed by the\n                    <jats:italic>Pkd1<\/jats:italic>\n                    gene, is present in a wide variety of cell types, but its cellular location, signaling mechanisms, and physiological functions are poorly understood. Here, by studying tamoxifen-inducible, endothelial cell (EC)-specific\n                    <jats:italic>Pkd1<\/jats:italic>\n                    knockout (\n                    <jats:italic>Pkd1<\/jats:italic>\n                    ecKO) mice, we show that flow activates PC-1-mediated, Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -dependent cation currents in ECs. EC-specific PC-1 knockout attenuates flow-mediated arterial hyperpolarization and vasodilation. PC-1-dependent vasodilation occurs over the entire functional shear stress range and via the activation of endothelial nitric oxide synthase (eNOS) and intermediate (IK)- and small (SK)-conductance Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -activated K\n                    <jats:sup>+<\/jats:sup>\n                    channels. EC-specific PC-1 knockout increases systemic blood pressure without altering kidney anatomy. PC-1 coimmunoprecipitates with polycystin-2 (PC-2, PKD2), a TRP polycystin channel, and clusters of both proteins locate in nanoscale proximity in the EC plasma membrane. Knockout of either PC-1 or PC-2 (\n                    <jats:italic>Pkd2<\/jats:italic>\n                    ecKO mice) abolishes surface clusters of both PC-1 and PC-2 in ECs. Single knockout of PC-1 or PC-2 or double knockout of PC-1 and PC-2 (\n                    <jats:italic>Pkd1<\/jats:italic>\n                    \/\n                    <jats:italic>Pkd2<\/jats:italic>\n                    ecKO mice) similarly attenuates flow-mediated vasodilation. Flow stimulates nonselective cation currents in ECs that are similarly inhibited by either PC-1 or PC-2 knockout or by interference peptides corresponding to the C-terminus coiled-coil domains present in PC-1 or PC-2. In summary, we show that PC-1 regulates arterial contractility through the formation of an interdependent signaling complex with PC-2 in ECs. Flow stimulates PC-1\/PC-2 clusters in the EC plasma membrane, leading to eNOS, IK channel, and SK channel activation, vasodilation, and a reduction in blood pressure.\n                  <\/jats:p>","DOI":"10.7554\/elife.74765","type":"journal-article","created":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T05:15:13Z","timestamp":1646111713000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.74765","source":"Crossref","is-referenced-by-count":39,"title":["A plasma membrane-localized polycystin-1\/polycystin-2 complex in endothelial cells elicits vasodilation"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2875-0677","authenticated-orcid":true,"given":"Charles E","family":"MacKay","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0011qv509","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Physiology, University of Tennessee Health Science Center","place":["Memphis, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miranda","family":"Floen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0011qv509","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Physiology, University of Tennessee Health Science Center","place":["Memphis, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Dennis","family":"Leo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0011qv509","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Physiology, University of Tennessee Health Science Center","place":["Memphis, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquibul","family":"Hasan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0011qv509","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Physiology, University of Tennessee Health Science Center","place":["Memphis, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessa AC","family":"Garrud","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0011qv509","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Physiology, University of Tennessee Health Science Center","place":["Memphis, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Fern\u00e1ndez-Pe\u00f1a","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0011qv509","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Physiology, University of Tennessee Health Science Center","place":["Memphis, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Purnima","family":"Singh","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0011qv509","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Physiology, University of Tennessee Health Science Center","place":["Memphis, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kafait U","family":"Malik","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0011qv509","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Physiology, University of Tennessee Health Science Center","place":["Memphis, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1505-3335","authenticated-orcid":true,"given":"Jonathan H","family":"Jaggar","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0011qv509","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Physiology, University of Tennessee Health Science Center","place":["Memphis, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2022,3,1]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1161\/CIRCRESAHA.108.192765","article-title":"Ciliary polycystin-2 is a mechanosensitive calcium channel involved in nitric oxide signaling cascades","volume":"104","author":"AbouAlaiwi","year":"2009","journal-title":"Circulation Research"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"2339","DOI":"10.1113\/JP273255","article-title":"Inwardly rectifying K+ channels are major contributors to flow-induced vasodilatation in resistance arteries","volume":"595","author":"Ahn","year":"2017","journal-title":"The Journal of Physiology"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"1624","DOI":"10.1161\/01.cir.91.6.1624","article-title":"Loss of flow-dependent coronary artery dilatation in patients with hypertension","volume":"91","author":"Antony","year":"1995","journal-title":"Circulation"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"E2363","DOI":"10.1073\/pnas.1517066113","article-title":"Function and regulation of TRPP2 ion channel revealed by a gain-of-function mutant","volume":"113","author":"Arif Pavel","year":"2016","journal-title":"PNAS"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"25582","DOI":"10.1074\/jbc.M402829200","article-title":"The N-terminal extracellular domain is required for polycystin-1-dependent channel activity","volume":"279","author":"Babich","year":"2004","journal-title":"The Journal of Biological Chemistry"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1152\/physrev.00042.2007","article-title":"eNOS activation by physical forces: from short-term regulation of contraction to chronic remodeling of cardiovascular tissues","volume":"89","author":"Balligand","year":"2009","journal-title":"Physiological Reviews"},{"key":"bib7","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-018-0047-y","article-title":"Polycystic kidney disease","volume":"4","author":"Bergmann","year":"2018","journal-title":"Nature Reviews. Disease Primers"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1111\/j.1365-2818.2006.01706.x","article-title":"A guided tour into subcellular colocalization analysis in light microscopy","volume":"224","author":"Bolte","year":"2006","journal-title":"Journal of Microscopy"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"12174","DOI":"10.1073\/pnas.211191098","article-title":"Cardiovascular, skeletal, and renal defects in mice with a targeted disruption of the Pkd1 gene","volume":"98","author":"Boulter","year":"2001","journal-title":"PNAS"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"2323","DOI":"10.1161\/CIRCULATIONAHA.108.846634","article-title":"Genetic deficit of SK3 and IK1 channels disrupts the endothelium-derived hyperpolarizing factor vasodilator pathway and causes hypertension","volume":"119","author":"Br\u00e4hler","year":"2009","journal-title":"Circulation"},{"key":"bib11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2019.109490","article-title":"Polycystin 2: A calcium channel, channel partner, and regulator of calcium homeostasis in ADPKD","volume":"66","author":"Brill","year":"2020","journal-title":"Cellular Signalling"},{"key":"bib12","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.42628","article-title":"Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure","volume":"7","author":"Bulley","year":"2018","journal-title":"eLife"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1093\/hmg\/4.4.575","article-title":"Analysis of the genomic sequence for the autosomal dominant polycystic kidney disease (PKD1) gene predicts the presence of a leucine-rich repeat. The American PKD1 Consortium (APKD1 Consortium)","volume":"4","author":"Burn","year":"1995","journal-title":"Human Molecular Genetics"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"4338","DOI":"10.1091\/mbc.E10-05-0407","article-title":"Polycystin-1 surface localization is stimulated by polycystin-2 and cleavage at the G protein-coupled receptor proteolytic site","volume":"21","author":"Chapin","year":"2010","journal-title":"Molecular Biology of the Cell"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1053\/j.ackd.2010.01.001","article-title":"Hypertension in autosomal dominant polycystic kidney disease","volume":"17","author":"Chapman","year":"2010","journal-title":"Advances in Chronic Kidney Disease"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1152\/physrev.1995.75.3.519","article-title":"Flow-mediated endothelial mechanotransduction","volume":"75","author":"Davies","year":"1995","journal-title":"Physiological Reviews"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1038\/nature12832","article-title":"Direct recording and molecular identification of the calcium channel of primary cilia","volume":"504","author":"DeCaen","year":"2013","journal-title":"Nature"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1038\/nature12833","article-title":"Primary cilia are specialized calcium signalling organelles","volume":"504","author":"Delling","year":"2013","journal-title":"Nature"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1038\/nature17426","article-title":"Primary cilia are not calcium-responsive mechanosensors","volume":"531","author":"Delling","year":"2016","journal-title":"Nature"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1096\/fj.03-0319fje","article-title":"Gating of the polycystin ion channel signaling complex in neurons and kidney cells","volume":"18","author":"Delmas","year":"2004","journal-title":"FASEB Journal"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1038\/21224","article-title":"Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation","volume":"399","author":"Dimmeler","year":"1999","journal-title":"Nature"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1152\/physrev.00026.2014","article-title":"Transient receptor potential channels in the vasculature","volume":"95","author":"Earley","year":"2015","journal-title":"Physiological Reviews"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"28471","DOI":"10.1074\/jbc.M803834200","article-title":"Identification and functional characterization of an N-terminal oligomerization domain for polycystin-2","volume":"283","author":"Feng","year":"2008","journal-title":"The Journal of Biological Chemistry"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1007\/s00424-009-0767-7","article-title":"Molecular mechanisms underlying the activation of eNOS","volume":"459","author":"Fleming","year":"2010","journal-title":"Pflugers Archiv"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1681\/ASN.V115814","article-title":"Cellular and subcellular distribution of polycystin-2, the protein product of the PKD2 gene","volume":"11","author":"Foggensteiner","year":"2000","journal-title":"Journal of the American Society of Nephrology"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1038\/21218","article-title":"Regulation of endothelium-derived nitric oxide production by the protein kinase Akt","volume":"399","author":"Fulton","year":"1999","journal-title":"Nature"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/s0272-6386(12)80051-5","article-title":"Autosomal dominant polycystic kidney disease--more than a renal disease","volume":"16","author":"Gabow","year":"1990","journal-title":"American Journal of Kidney Diseases"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1172\/JCI76972","article-title":"Polycystin-1 maturation requires polycystin-2 in a dose-dependent manner","volume":"125","author":"Gainullin","year":"2015","journal-title":"The Journal of Clinical Investigation"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1111\/bph.14522","article-title":"Endothelial NOS: perspective and recent developments","volume":"176","author":"Garcia","year":"2019","journal-title":"British Journal of Pharmacology"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1111\/j.1476-5381.2010.01148.x","article-title":"EDHF: spreading the influence of the endothelium","volume":"164","author":"Garland","year":"2011","journal-title":"British Journal of Pharmacology"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1038\/nsmb.3343","article-title":"Structure of the polycystic kidney disease TRP channel Polycystin-2 (PC2)","volume":"24","author":"Grieben","year":"2017","journal-title":"Nature Structural & Molecular Biology"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1681\/ASN.V84616","article-title":"Vascular expression of polycystin","volume":"8","author":"Griffin","year":"1997","journal-title":"Journal of the American Society of Nephrology"},{"key":"bib33","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.60684","article-title":"The heteromeric PC-1\/PC-2 polycystin complex is activated by the PC-1 N-terminus","volume":"9","author":"Ha","year":"2020","journal-title":"eLife"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1038\/35050128","article-title":"Co-assembly of polycystin-1 and -2 produces unique cation-permeable currents","volume":"408","author":"Hanaoka","year":"2000","journal-title":"Nature"},{"key":"bib35","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2020.109640","article-title":"Polycystins as components of large multiprotein complexes of polycystin interactors","volume":"72","author":"Hardy","year":"2020","journal-title":"Cellular Signalling"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1038\/ng0695-151","article-title":"The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains","volume":"10","author":"Hughes","year":"1995","journal-title":"Nature Genetics"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"C235","DOI":"10.1152\/ajpcell.2000.278.2.C235","article-title":"Calcium sparks in smooth muscle","volume":"278","author":"Jaggar","year":"2000","journal-title":"American Journal of Physiology. Cell Physiology"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1093\/biosci\/biu181","article-title":"Electrical Signaling in Motile and Primary Cilia","volume":"64","author":"Kleene","year":"2014","journal-title":"Bioscience"},{"key":"bib39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0214053","article-title":"The TRPP2-dependent channel of renal primary cilia also requires TRPM3","volume":"14","author":"Kleene","year":"2019","journal-title":"PLOS ONE"},{"key":"bib40","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.33183","article-title":"Polycystin-2 is an essential ion channel subunit in the primary cilium of the renal collecting duct epithelium","volume":"7","author":"Liu","year":"2018","journal-title":"eLife"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/ki.2014.241","article-title":"Polycystin deficiency induces dopamine-reversible alterations in flow-mediated dilatation and vascular nitric oxide release in humans","volume":"87","author":"Lorthioir","year":"2015","journal-title":"Kidney International"},{"key":"bib42","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.56655","article-title":"Intravascular flow stimulates PKD2 (polycystin-2) channels in endothelial cells to reduce blood pressure","volume":"9","author":"MacKay","year":"2020","journal-title":"eLife"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1053\/j.ajkd.2004.04.026","article-title":"Exercise blood pressure, cardiac structure, and diastolic function in young normotensive patients with polycystic kidney disease: a prehypertensive state","volume":"44","author":"Martinez-Vea","year":"2004","journal-title":"American Journal of Kidney Diseases"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1038\/ng1076","article-title":"Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells","volume":"33","author":"Nauli","year":"2003","journal-title":"Nature Genetics"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1161\/CIRCULATIONAHA.107.710111","article-title":"Endothelial cilia are fluid shear sensors that regulate calcium signaling and nitric oxide production through polycystin-1","volume":"117","author":"Nauli","year":"2008","journal-title":"Circulation"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"C3","DOI":"10.1152\/ajpcell.1990.259.1.C3","article-title":"Calcium channels, potassium channels, and voltage dependence of arterial smooth muscle tone","volume":"259","author":"Nelson","year":"1990","journal-title":"The American Journal of Physiology"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"20763","DOI":"10.1074\/jbc.M107788200","article-title":"Identification, characterization, and localization of a novel kidney polycystin-1-polycystin-2 complex","volume":"277","author":"Newby","year":"2002","journal-title":"The Journal of Biological Chemistry"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1006\/bbrc.1998.9514","article-title":"The polycystic kidney disease-1 protein, polycystin-1, binds and activates heterotrimeric G-proteins in vitro","volume":"251","author":"Parnell","year":"1998","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1097\/00041552-200309000-00006","article-title":"The renal cell primary cilium functions as a flow sensor","volume":"12","author":"Praetorius","year":"2003","journal-title":"Current Opinion in Nephrology and Hypertension"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/ng0697-179","article-title":"PKD1 interacts with PKD2 through a probable coiled-coil domain","volume":"16","author":"Qian","year":"1997","journal-title":"Nature Genetics"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"16981","DOI":"10.1073\/pnas.252484899","article-title":"Cleavage of polycystin-1 requires the receptor for egg jelly domain and is disrupted by human autosomal-dominant polycystic kidney disease 1-associated mutations","volume":"99","author":"Qian","year":"2002","journal-title":"PNAS"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"2143","DOI":"10.1681\/ASN.2006121387","article-title":"Comprehensive molecular diagnostics in autosomal dominant polycystic kidney disease","volume":"18","author":"Rossetti","year":"2007","journal-title":"Journal of the American Society of Nephrology"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1016\/j.cell.2016.09.048","article-title":"The Structure of the Polycystic Kidney Disease Channel PKD2 in Lipid Nanodiscs","volume":"167","author":"Shen","year":"2016","journal-title":"Cell"},{"key":"bib54","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat9819","article-title":"Structure of the human PKD1-PKD2 complex","volume":"361","author":"Su","year":"2018","journal-title":"Science (New York, N.Y.)"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1161\/01.RES.0000081980.63146.69","article-title":"Altered expression of small-conductance Ca2+-activated K+ (SK3) channels modulates arterial tone and blood pressure","volume":"93","author":"Taylor","year":"2003","journal-title":"Circulation Research"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1016\/S0140-6736(07)60601-1","article-title":"Autosomal dominant polycystic kidney disease","volume":"369","author":"Torres","year":"2007","journal-title":"Lancet (London, England)"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"6965","DOI":"10.1073\/pnas.94.13.6965","article-title":"Homo- and heterodimeric interactions between the gene products of PKD1 and PKD2","volume":"94","author":"Tsiokas","year":"1997","journal-title":"PNAS"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1681\/ASN.V1051020","article-title":"Ambulatory blood pressure and left ventricular mass in normotensive patients with autosomal dominant polycystic kidney disease","volume":"10","author":"Valero","year":"1999","journal-title":"Journal of the American Society of Nephrology"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1098\/rstb.1994.0023","article-title":"The endothelium: maestro of the blood circulation","volume":"343","author":"Vane","year":"1993","journal-title":"Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1038\/nature09002","article-title":"Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis","volume":"465","author":"Wang","year":"2010","journal-title":"Nature"},{"key":"bib61","doi-asserted-by":"publisher","first-page":"4527","DOI":"10.1172\/JCI87343","article-title":"Endothelial cation channel PIEZO1 controls blood pressure by mediating flow-induced ATP release","volume":"126","author":"Wang","year":"2016","journal-title":"The Journal of Clinical Investigation"},{"key":"bib62","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201948336","article-title":"The ion channel function of polycystin-1 in the polycystin-1\/polycystin-2 complex","volume":"20","author":"Wang","year":"2019","journal-title":"EMBO Reports"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1016\/j.cell.2018.03.076","article-title":"GPR68 Senses Flow and Is Essential for Vascular Physiology","volume":"173","author":"Xu","year":"2018","journal-title":"Cell"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1126\/science.1222538","article-title":"Cilia at the node of mouse embryos sense fluid flow for left-right determination via Pkd2","volume":"338","author":"Yoshiba","year":"2012","journal-title":"Science (New York, N.Y.)"},{"key":"bib65","doi-asserted-by":"publisher","first-page":"11558","DOI":"10.1073\/pnas.0903684106","article-title":"Structural and molecular basis of the assembly of the TRPP2\/PKD1 complex","volume":"106","author":"Yu","year":"2009","journal-title":"PNAS"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1146\/annurev.physiol.70.113006.100621","article-title":"Polycystins and primary cilia: primers for cell cycle progression","volume":"71","author":"Zhou","year":"2009","journal-title":"Annual Review of Physiology"},{"key":"bib67","doi-asserted-by":"publisher","first-page":"10133","DOI":"10.1073\/pnas.1017669108","article-title":"Structural model of the TRPP2\/PKD1 C-terminal coiled-coil complex produced by a combined computational and experimental approach","volume":"108","author":"Zhu","year":"2011","journal-title":"PNAS"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/74765\/elife-74765-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/74765\/elife-74765-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/74765","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:11:37Z","timestamp":1697058697000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/74765"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,1]]},"references-count":67,"alternative-id":["10.7554\/eLife.74765"],"URL":"https:\/\/doi.org\/10.7554\/elife.74765","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.10.16.464653","asserted-by":"subject"},{"id-type":"doi","id":"10.1101\/2021.10.16.464653","asserted-by":"object"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.74765.sa2","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.74765.sa0","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.74765.sa1","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,1]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"e74765"}}