دورية أكاديمية
Low potassium activation of proximal mTOR/AKT signaling is mediated by Kir4.2.
العنوان: | Low potassium activation of proximal mTOR/AKT signaling is mediated by Kir4.2. |
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المؤلفون: | Zhang Y; Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Vanderbilt Center for Kidney Disease, Nashville, TN, USA., Bock F; Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Vanderbilt Center for Kidney Disease, Nashville, TN, USA., Ferdaus M; Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, USA., Arroyo JP; Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Vanderbilt Center for Kidney Disease, Nashville, TN, USA., L Rose K; Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.; Mass Spectrometry Research Center, Vanderbilt University School of Medicine, Nashville, TN, USA., Patel P; Mass Spectrometry Research Center, Vanderbilt University School of Medicine, Nashville, TN, USA., Denton JS; Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, USA., Delpire E; Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, USA., Weinstein AM; Department of Physiology and Biophysics, Weil Medical College, New York, NY, USA., Zhang MZ; Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Vanderbilt Center for Kidney Disease, Nashville, TN, USA., Harris RC; Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Vanderbilt Center for Kidney Disease, Nashville, TN, USA.; Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA., Terker AS; Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. Andrew.s.terker@vumc.org.; Vanderbilt Center for Kidney Disease, Nashville, TN, USA. Andrew.s.terker@vumc.org. |
المصدر: | Nature communications [Nat Commun] 2024 Jun 17; Vol. 15 (1), pp. 5144. Date of Electronic Publication: 2024 Jun 17. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [London] : Nature Pub. Group |
مواضيع طبية MeSH: | Proto-Oncogene Proteins c-akt*/metabolism , Potassium Channels, Inwardly Rectifying*/metabolism , Potassium Channels, Inwardly Rectifying*/genetics , TOR Serine-Threonine Kinases*/metabolism , Signal Transduction* , Mice, Knockout* , Potassium*/metabolism , Kidney Tubules, Proximal*/metabolism , Mechanistic Target of Rapamycin Complex 2*/metabolism , Mechanistic Target of Rapamycin Complex 2*/genetics, Animals ; Mice ; Phosphorylation ; Male ; Chlorides/metabolism ; Mice, Inbred C57BL |
مستخلص: | The renal epithelium is sensitive to changes in blood potassium (K + ). We identify the basolateral K + channel, Kir4.2, as a mediator of the proximal tubule response to K + deficiency. Mice lacking Kir4.2 have a compensated baseline phenotype whereby they increase their distal transport burden to maintain homeostasis. Upon dietary K + depletion, knockout animals decompensate as evidenced by increased urinary K + 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 + response, which is blunted in Kir4.2 knockouts. Lastly, we demonstrate in isolated tubules that AKT phosphorylation in response to low K + depends upon mTORC2 activation by secondary changes in Cl - transport. Data support a proximal role for cell Cl - which, as it does along the distal nephron, responds to K + changes to activate kinase signaling. (© 2024. The Author(s).) |
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معلومات مُعتمدة: | T32 DK007569 United States DK NIDDK NIH HHS; K08 DK135931 United States DK NIDDK NIH HHS; DP5OD033412 U.S. Department of Health & Human Services | National Institutes of Health (NIH); K08 DK134879 United States DK NIDDK NIH HHS; P30 DK020593 United States DK NIDDK NIH HHS; P30 CA068485 United States CA NCI NIH HHS; P30 DK114809 United States DK NIDDK NIH HHS; R01 DK062794 United States DK NIDDK NIH HHS; R01 DK029857 United States DK NIDDK NIH HHS; DP5 OD033412 United States OD NIH HHS; R01 DK095785 United States DK NIDDK NIH HHS |
المشرفين على المادة: | EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) 0 (Potassium Channels, Inwardly Rectifying) EC 2.7.11.1 (TOR Serine-Threonine Kinases) RWP5GA015D (Potassium) EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2) 0 (Kcnj10 (channel)) EC 2.7.1.1 (mTOR protein, mouse) 0 (Chlorides) |
تواريخ الأحداث: | Date Created: 20240617 Date Completed: 20240617 Latest Revision: 20240620 |
رمز التحديث: | 20240620 |
مُعرف محوري في PubMed: | PMC11183202 |
DOI: | 10.1038/s41467-024-49562-w |
PMID: | 38886379 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2041-1723 |
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DOI: | 10.1038/s41467-024-49562-w |