{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T22:37:06Z","timestamp":1791153426498,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,1,9]],"date-time":"2012-01-09T00:00:00Z","timestamp":1326067200000},"content-version":"vor","delay-in-days":1317,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology of the Cell"],"published-print":{"date-parts":[[2008,6]]},"abstract":"<jats:p><jats:italic>Background information<\/jats:italic>. Mercurials inhibit AQPs (aquaporins), and site\u2010directed mutagenesis has identified Cys<jats:sup>189<\/jats:sup> as a site of the mercurial inhibition of AQP1. On the other hand, AQP4 has been considered to be a mercury\u2010insensitive water channel because it does not have the reactive cysteine residue corresponding to Cys<jats:sup>189<\/jats:sup> of AQP1. Indeed, the osmotic water permeability (<jats:italic>P<\/jats:italic><jats:sub>f<\/jats:sub>) of AQP4 expressed in various types of cells, including <jats:italic>Xenopus<\/jats:italic> oocytes, is not inhibited by HgCl<jats:sub>2<\/jats:sub>. To examine the direct effects of mercurials on AQP4 in a proteoliposome reconstitution system, His\u2010tagged rAPR4 (rat AQP4) M23 was expressed in <jats:italic>Saccharomyces cerevisiae<\/jats:italic>, purified with an Ni<jats:sup>2+<\/jats:sup>\u2010nitrilotriacetate affinity column, and reconstituted into liposomes with the dilution method.<\/jats:p><jats:p><jats:italic>Results<\/jats:italic>. The water permeability of AQP4 proteoliposomes with or without HgCl<jats:sub>2<\/jats:sub> was measured with a stopped\u2010flow apparatus. Surprisingly, the <jats:italic>P<\/jats:italic><jats:sub>f<\/jats:sub> of AQP4 proteoliposomes was significantly decreased by 5 \u03bcM HgCl<jats:sub>2<\/jats:sub> within 30 s, and this effect was completely reversed by 2\u2010mercaptoethanol. The dose\u2010 and time\u2010dependent inhibitory effects of Hg<jats:sup>2+<\/jats:sup> suggest that the sensitivity to mercury of AQP4 is different from that of AQP1. Site\u2010directed mutagenesis of six cysteine residues of AQP4 demonstrated that Cys<jats:sup>178<\/jats:sup>, which is located at loop D facing the intracellular side, is a target responding to Hg<jats:sup>2+<\/jats:sup>. We confirmed that AQP4 is reconstituted into liposome in a bidirectional orientation.<\/jats:p><jats:p><jats:italic>Conclusions<\/jats:italic>. Our results suggest that mercury inhibits the <jats:italic>P<\/jats:italic><jats:sub>f<\/jats:sub> of AQP4 by mechanisms different from those for AQP1 and that AQP4 may be gated by modification of a cysteine residue in cytoplasmic loop D.<\/jats:p>","DOI":"10.1042\/bc20070132","type":"journal-article","created":{"date-parts":[[2008,5,8]],"date-time":"2008-05-08T10:15:11Z","timestamp":1210241711000},"page":"355-363","source":"Crossref","is-referenced-by-count":74,"title":["Mercury chloride decreases the water permeability of aquaporin\u20104\u2010reconstituted proteoliposomes"],"prefix":"10.1111","volume":"100","author":[{"given":"Yoshinori","family":"Yukutake","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoji","family":"Tsuji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Hirano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Adachi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Fujihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Agre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Yasui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Suematsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,1,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.020818"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04321"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"3673","DOI":"10.1016\/S0021-9258(18)95862-X","article-title":"Studies on the chemistry of hemoglobin. 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