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Most relevant scientific articles
Research Groups
nagamori s, WiriYasermKul P, guarch me, oKuYama h, naKagomi s, tadagaKi K, nishinaKa Y, BodoY s, taKaFu- Ji K, oKuda s, KuroKaWa J, ohgaKi r, nunes V, Palacín m, Kanai Y. Novel cystine transporter in renal proximal tubule identified as a missing partner of cystinuria-relat- ed plasma membrane protein rBAT/SLC3A1. Proc Natl Acad Sci U S A. 2016 Jan 19;113(3):775-80. doi: 10.1073/ pnas.1519959113. Epub 2016 Jan 6.
esPino m, Font-llitJós m, Vilches c, salido e, Prat e, lóPeZ de heredia m, Palacín m, nunes V. Digenic Inher- itance in Cystinuria Mouse Model. PLoS One. 2015 Sep 11;10(9):e0137277. doi: 10.1371/journal.pone.0137277. eCollection 2015.
Highlights
Our activity has been focused in four research lines. At first instance, in collaboration with Rafael Artuch (U-703) we have progressed in phenotyping the first animal model of lysinuric Protein Intolerance (LPI). Tamoxifen-induced conditional knockout of y+LAT1 mimics the metabolic derangement of human LPI. In addition, this murine model shows immune ab- normalities like altered iron metabolism in mac- rophages. We are trying at present to elucidate the involved molecular mechanism.
Secondly, in collaboration with Virginia Nunes (U- 730) and Antonia Ribes (U-737) we have improved our knowledge on the molecular bases of renal re-absorption of amino acids. We had demonstrated digenic inheritance in rBAT- and b0,+AT-genetic ab- lation in mouse (Espino et al. 2015 PLoS One). We have also identified a second transporter (AGT1) that heterodimerizes with rBAT in kidney (Nagamori et al., 2016 PNAS). Because b0,+AT/rBAT and AGT1/ rBAT transports cystine, this second transporter is a candidate gene to be mutated in non-explained cas- es of cystinuria. Moreover, murine models with dou-
ble loss-of-function of LAT2 and TAT1, but not the single genetic ablation models, showed a dramatic hyperexcretion of neutral amino acids in urine sug- gesting functional cooperation of LAT2/4F2hc and TAT1 in renal reabsorption. We have also detect- ed urine hyperexcretion of organic acids in mouse models with aminoacidurias. Specifically, genetic ablation of basolateral transporters of cationic ami- no acids results in hyperexcretion of Krebs cycle in- termediates in urine.
In third place, we have identified, in collaboration with Virginia Nunes (U-730) and Isabel Varela (U-761), a HAT transporter involved in age related hearing loss. Genetic ablation of this transporter in mouse and functional mutations in human causes hearing loss.
Finally, we have identified a HAT transporter (verte- brate vLAT1/4F2hc) with high stability and promis- ing properties to solve the structure of a HAT trans- porter at subnanometric resolution.
Institution: Fundación privada Instituto de Recerca Biomédica (IRB-Barcelona) Contact: C/ Baldiri Reixac 10-12. 08028 Barcelona · Tel.: 93 403 71 98 / 9 E.mail: [email protected] · Website: http://www.irbbarcelona.org
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