{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T02:24:11Z","timestamp":1774319051383,"version":"3.50.1"},"reference-count":34,"publisher":"Proceedings of the National Academy of Sciences","issue":"46","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,11,14]]},"abstract":"<jats:p>\n                    The prohibitin (PHB)-domain proteins are membrane proteins that regulate a variety of biological activities, including mechanosensation, osmotic homeostasis, and cell signaling, although the mechanism of this regulation is unknown. We have studied two members of this large protein family, MEC-2, which is needed for touch sensitivity in\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    , and Podocin, a protein involved in the function of the filtration barrier in the mammalian kidney, and find that both proteins bind cholesterol. This binding requires the PHB domain (including palmitoylation sites within it) and part of the N-terminally adjacent hydrophobic domain that attaches the proteins to the inner leaflet of the plasma membrane. By binding to MEC-2 and Podocin, cholesterol associates with ion-channel complexes to which these proteins bind: DEG\/ENaC channels for MEC-2 and TRPC channels for Podocin. Both the MEC-2-dependent activation of mechanosensation and the Podocin-dependent activation of TRPC channels require cholesterol. Thus, MEC-2, Podocin, and probably many other PHB-domain proteins by binding to themselves, cholesterol, and target proteins regulate the formation and function of large protein\u2013cholesterol supercomplexes in the plasma membrane.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0607465103","type":"journal-article","created":{"date-parts":[[2006,11,1]],"date-time":"2006-11-01T20:26:04Z","timestamp":1162412764000},"page":"17079-17086","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":262,"title":["Podocin and MEC-2 bind cholesterol to regulate the activity of associated ion channels"],"prefix":"10.1073","volume":"103","author":[{"given":"Tobias B.","family":"Huber","sequence":"first","affiliation":[{"name":"*Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany;"}]},{"given":"Bernhard","family":"Schermer","sequence":"additional","affiliation":[{"name":"*Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany;"}]},{"given":"Roman Ulrich","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"*Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany;"}]},{"given":"Martin","family":"H\u00f6hne","sequence":"additional","affiliation":[{"name":"*Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany;"}]},{"given":"Malte","family":"Bartram","sequence":"additional","affiliation":[{"name":"*Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany;"}]},{"given":"Andrea","family":"Calixto","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Columbia University, New York, NY 10027-6902;"}]},{"given":"Henning","family":"Hagmann","sequence":"additional","affiliation":[{"name":"*Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany;"}]},{"given":"Christian","family":"Reinhardt","sequence":"additional","affiliation":[{"name":"*Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany;"},{"name":"University Hospital M\u00fcnster, D-48129 M\u00fcnster, Germany;"}]},{"given":"Fabienne","family":"Koos","sequence":"additional","affiliation":[{"name":"*Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany;"}]},{"given":"Karl","family":"Kunzelmann","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Regensburg, 93053 Regensburg, Germany;"}]},{"given":"Elena","family":"Shirokova","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, German Institute of Human Nutrition, 14558 Nuthetal, Germany;"}]},{"given":"Dietmar","family":"Krautwurst","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, German Institute of Human Nutrition, 14558 Nuthetal, Germany;"}]},{"given":"Christian","family":"Harteneck","sequence":"additional","affiliation":[{"name":"Pharmacology, Charit\u00e9, University of Berlin, 14050 Berlin, Germany;"}]},{"given":"Matias","family":"Simons","sequence":"additional","affiliation":[{"name":"*Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany;"}]},{"given":"Hermann","family":"Pavenst\u00e4dt","sequence":"additional","affiliation":[{"name":"University Hospital M\u00fcnster, D-48129 M\u00fcnster, Germany;"}]},{"given":"Dontscho","family":"Kerjaschki","sequence":"additional","affiliation":[{"name":"**Department of Pathology, University of Vienna, A-1010 Vienna, Austria; and"}]},{"given":"Christoph","family":"Thiele","sequence":"additional","affiliation":[{"name":"Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany"}]},{"given":"Gerd","family":"Walz","sequence":"additional","affiliation":[{"name":"*Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany;"}]},{"given":"Martin","family":"Chalfie","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Columbia University, New York, NY 10027-6902;"}]},{"given":"Thomas","family":"Benzing","sequence":"additional","affiliation":[{"name":"*Renal Division, University Hospital Freiburg, 79106 Freiburg, Germany;"}]}],"member":"341","published-online":{"date-parts":[[2006,11,14]]},"reference":[{"key":"e_1_3_5_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/27.1.229"},{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2005.00318.x"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000130167.30769.55"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.36.061802.101708"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.moh.0000132240.20671.33"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/378292a0"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/74166"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg360"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2004.10.030"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/4151039a"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1362"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64357-X"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80057-X"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5438.312"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1592"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1106215"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/71366"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M513720200"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1080\/10409239991209309"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.092999"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M411508200"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01205"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1996.67010046.x"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.11.8062"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(98)00532-0"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/00041433-200406000-00005"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00003.2003"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C100452200"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200323884"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/11354"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(91)90094-A"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0020280"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/367470a0"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0606894103"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0607465103","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T15:43:59Z","timestamp":1649778239000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0607465103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,11,14]]},"references-count":34,"journal-issue":{"issue":"46","published-print":{"date-parts":[[2006,11,14]]}},"alternative-id":["10.1073\/pnas.0607465103"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0607465103","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1048334.500244","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1048334.505922","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,11,14]]},"assertion":[{"value":"2006-11-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}