{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:26:41Z","timestamp":1790364401198,"version":"4.1.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:p>\n                    <jats:bold>Background<\/jats:bold>\n                    Reabsorption of amino acids (AAs) across the renal proximal tubule is crucial for intracellular and whole organism AA homeostasis. Although the luminal transport step is well understood, with several diseases caused by dysregulation of this process, the basolateral transport step is not understood. In humans, only cationic aminoaciduria due to malfunction of the basolateral transporter y\n                    <jats:sup>+<\/jats:sup>\n                    LAT1\/CD98hc (SLC7A7\/SLC3A2), which mediates the export of cationic AAs, has been described. Thus, the physiologic roles of basolateral transporters of neutral AAs, such as the antiporter LAT2\/CD98hc (SLC7A8\/SLC3A2), a heterodimer that exports most neutral AAs, and the uniporter TAT1 (SLC16A10), which exports only aromatic AAs, remain unclear. Functional cooperation between TAT1 and LAT2\/CD98hc has been suggested by\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    studies but has not been evaluated\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    .\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods<\/jats:bold>\n                    To study the functional relationship of TAT1 and LAT2\/CD98hc\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    , we generated a double-knockout mouse model lacking TAT1 and LAT2, the catalytic subunit of LAT2\/CD98hc (dKO LAT2-TAT1 mice).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results<\/jats:bold>\n                    Compared with mice lacking only TAT1 or LAT2, dKO LAT2-TAT1 mice lost larger amounts of aromatic and other neutral AAs in their urine due to a tubular reabsorption defect. Notably, dKO mice also displayed decreased tubular reabsorption of cationic AAs and increased expression of y\n                    <jats:sup>+<\/jats:sup>\n                    LAT1\/CD98hc.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions<\/jats:bold>\n                    The LAT2\/CD98hc and TAT1 transporters functionally cooperate\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    , and y\n                    <jats:sup>+<\/jats:sup>\n                    LAT1\/CD98hc may compensate for the loss of LAT2\/CD98hc and TAT1, functioning as a neutral AA exporter at the expense of some urinary loss of cationic AAs. Cooperative and compensatory mechanisms of AA transporters may explain the lack of basolateral neutral aminoacidurias in humans.\n                  <\/jats:p>","DOI":"10.1681\/asn.2017111205","type":"journal-article","created":{"date-parts":[[2018,4,2]],"date-time":"2018-04-02T09:45:26Z","timestamp":1522662326000},"page":"1624-1635","source":"Crossref","is-referenced-by-count":32,"title":["Cooperation of Antiporter LAT2\/CD98hc with Uniporter TAT1 for Renal Reabsorption of Neutral Amino Acids"],"prefix":"10.1681","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2695-2128","authenticated-orcid":false,"given":"Clara","family":"Vilches","sequence":"first","affiliation":[{"name":"Molecular Genetics Laboratory, Genes Disease and Therapy Program, Institut d'Investigaci\u00f3 Biom\u00e8dica de Bellvitge (IDIBELL), L\u2019Hospitalet de Llobregat, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Boiadjieva-Kn\u00f6pfel","sequence":"additional","affiliation":[{"name":"Department of Physiology,"},{"name":"Zurich Center for Integrative Human Physiology (ZIHP), and"},{"name":"Swiss National Centre of Competence in Research (NCCR), Kidney Control of Homeostasis (Kidney.CH), University of Zurich, Zurich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9261-4373","authenticated-orcid":false,"given":"Susanna","family":"Bodoy","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, Biology Faculty, University of Barcelona, Barcelona, Spain;"},{"name":"Molecular Medicine Unit, Amino acid transporters and disease group, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0091-7380","authenticated-orcid":false,"given":"Simone","family":"Camargo","sequence":"additional","affiliation":[{"name":"Department of Physiology,"},{"name":"Zurich Center for Integrative Human Physiology (ZIHP), and"},{"name":"Swiss National Centre of Competence in Research (NCCR), Kidney Control of Homeostasis (Kidney.CH), University of Zurich, Zurich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2826-9565","authenticated-orcid":false,"given":"Miguel","family":"L\u00f3pez de Heredia","sequence":"additional","affiliation":[{"name":"Molecular Genetics Laboratory, Genes Disease and Therapy Program, Institut d'Investigaci\u00f3 Biom\u00e8dica de Bellvitge (IDIBELL), L\u2019Hospitalet de Llobregat, Spain;"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER) \u2013 U730, U731, U703, 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Amino acid transporters and disease group, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain;"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM) \u2013 CB07\/08\/0017, Instituto de Salud Carlos III (ISCIII), Madrid, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3250-9824","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Verrey","sequence":"additional","affiliation":[{"name":"Department of Physiology,"},{"name":"Zurich Center for Integrative Human Physiology (ZIHP), and"},{"name":"Swiss National Centre of Competence in Research (NCCR), Kidney Control of Homeostasis (Kidney.CH), University of Zurich, Zurich, 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