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We identify the basolateral K\n                    <jats:sup>+<\/jats:sup>\n                    channel, Kir4.2, as a mediator of the proximal tubule response to K\n                    <jats:sup>+<\/jats:sup>\n                    deficiency. Mice lacking Kir4.2 have a compensated baseline phenotype whereby they increase their distal transport burden to maintain homeostasis. Upon dietary K\n                    <jats:sup>+<\/jats:sup>\n                    depletion, knockout animals decompensate as evidenced by increased urinary K\n                    <jats:sup>+<\/jats:sup>\n                    excretion and development of a proximal renal tubular acidosis. Potassium wasting is not proximal in origin but is caused by higher ENaC activity and depends upon increased distal sodium delivery. Three-dimensional imaging reveals Kir4.2 knockouts fail to undergo proximal tubule expansion, while the distal convoluted tubule response is exaggerated. AKT signaling mediates the dietary K\n                    <jats:sup>+<\/jats:sup>\n                    response, which is blunted in Kir4.2 knockouts. Lastly, we demonstrate in isolated tubules that AKT phosphorylation in response to low K\n                    <jats:sup>+<\/jats:sup>\n                    depends upon mTORC2 activation by secondary changes in Cl\n                    <jats:sup>-<\/jats:sup>\n                    transport. Data support a proximal role for cell Cl\n                    <jats:sup>-<\/jats:sup>\n                    which, as it does along the distal nephron, responds to K\n                    <jats:sup>+<\/jats:sup>\n                    changes to activate kinase signaling.\n                  <\/jats:p>","DOI":"10.1038\/s41467-024-49562-w","type":"journal-article","created":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T06:09:01Z","timestamp":1718604541000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Low potassium activation of proximal mTOR\/AKT signaling is mediated by Kir4.2"],"prefix":"10.1038","volume":"15","author":[{"given":"Yahua","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Bock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Ferdaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5992-5011","authenticated-orcid":false,"given":"Juan Pablo","family":"Arroyo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristie","family":"L Rose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Purvi","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerod S.","family":"Denton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Delpire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan M.","family":"Weinstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0980-2419","authenticated-orcid":false,"given":"Ming-Zhi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond C.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1498-9043","authenticated-orcid":false,"given":"Andrew S.","family":"Terker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,17]]},"reference":[{"key":"49562_CR1","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1172\/JCI112973","volume":"79","author":"JP Tolins","year":"1987","unstructured":"Tolins, J. 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