{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:28:45Z","timestamp":1787725725452,"version":"build-2784847793"},"reference-count":50,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2011,5]]},"abstract":"<jats:p> We report the novel, heterozygous AE1 mutation R730C associated with dominant, overhydrated, cation leak stomatocytosis and well-compensated anemia. Parallel elevations of red blood cell cation leak and ouabain-sensitive Na<jats:sup>+<\/jats:sup> efflux (pump activity) were apparently unaccompanied by increased erythroid cation channel-like activity, and defined ouabain-insensitive Na<jats:sup>+<\/jats:sup> efflux pathways of nystatin-treated cells were reduced. Epitope-tagged AE1 R730C at the Xenopus laevis oocyte surface exhibited severely reduced Cl<jats:sup>\u2212<\/jats:sup> transport insensitive to rescue by glycophorin A (GPA) coexpression or by methanethiosulfonate (MTS) treatment. AE1 mutant R730K preserved Cl<jats:sup>\u2212<\/jats:sup> transport activity, but R730 substitution with I, E, or H inactivated Cl<jats:sup>\u2212<\/jats:sup> transport. AE1 R730C expression substantially increased endogenous oocyte Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-ATPase-mediated <jats:sup>86<\/jats:sup>Rb<jats:sup>+<\/jats:sup> influx, but ouabain-insensitive flux was minimally increased and GPA-insensitive. The reduced AE1 R730C-mediated sulfate influx did not exhibit the wild-type pattern of stimulation by acidic extracellular pH (pH<jats:sub>o<\/jats:sub>) and, unexpectedly, was partially rescued by exposure to sodium 2-sulfonatoethyl methanethiosulfonate (MTSES) but not to 2-aminoethyl methanethiosulfonate hydrobromide (MTSEA) or 2-(trimethylammonium)ethyl methanethiosulfonate bromide (MTSET). AE1 R730E correspondingly exhibited acid pH<jats:sub>o<\/jats:sub>-stimulated sulfate uptake at rates exceeding those of wild-type AE1 and AE1 R730K, whereas mutants R730I and R730H were inactive and pH<jats:sub>o<\/jats:sub> insensitive. MTSES-treated oocytes expressing AE1 R730C and untreated oocytes expressing AE1 R730E also exhibited unprecedented stimulation of Cl<jats:sup>\u2212<\/jats:sup> influx by acid pH<jats:sub>o<\/jats:sub>. Thus recombinant cation-leak stomatocytosis mutant AE1 R730C exhibits severely reduced anion transport unaccompanied by increased Rb<jats:sup>+<\/jats:sup> and Li<jats:sup>+<\/jats:sup> influxes. Selective rescue of acid pH<jats:sub>o<\/jats:sub>-stimulated sulfate uptake and conferral of acid pH<jats:sub>o<\/jats:sub>-stimulated Cl<jats:sup>\u2212<\/jats:sup> influx, by AE1 R730E and MTSES-treated R730C, define residue R730 as critical to selectivity and regulation of anion transport by AE1. <\/jats:p>","DOI":"10.1152\/ajpcell.00447.2010","type":"journal-article","created":{"date-parts":[[2011,1,6]],"date-time":"2011-01-06T03:57:10Z","timestamp":1294286230000},"page":"C1034-C1046","source":"Crossref","is-referenced-by-count":34,"title":["Functional characterization and modified rescue of novel AE1 mutation R730C associated with overhydrated cation leak stomatocytosis"],"prefix":"10.1152","volume":"300","author":[{"given":"Andrew K.","family":"Stewart","sequence":"first","affiliation":[{"name":"Divisions of 1Nephrology and"},{"name":"Departments of 4Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabhakar 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