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Most relevant scientific articles
• Structural bases for the interaction and stabilization of the human amino acid transporter LAT2 with its anci- llary protein 4F2hc . rosell a, meury m, álVarez-marimon e, costa m, pérez-cano l, zorzano a, FernánDez-recio J*, palacín m*, FotiaDis D*. (*; correspondence authors) Proc Natl Acad Sci U S A . 2014 Feb 25;111(8):2966-71 . doi: 10 .1073/pnas .1323779111 . Epub 2014 Feb 10 . PMID: 24516142
• Detergent-induced stabilization and improved 3D map of the human heteromeric amino acid transporter 4F2hc-LAT2 . meury m, costa m, HarDer D, stauFFer m, JecKelmann Jm, brüHlmann b, rosell a, ilGü H, KoVar K, palacín m*, FotiaDis D* . (*; correspondence authors) PLoS One . 2014 Oct 9;9(10):e109882 . doi: 10 .1371/ journal .pone .0109882 . eCollection 2014 .PMID: 25299125 [PubMed - in process]
• Two novel mutations in the BCKDK (branched-chain keto-acid dehydrogenase kinase) gene are responsible for a neurobehavioral deficit in two pediatric unrelated patients . García-cazorla a, oyarzabal a, Fort J, robles c, casteJón e, ruiz-sala p, boDoy s, merinero b, lopez-sala a, Dopazo J, nunes V, uGarte m, artucH r*, palacín m*, roDríGuez-pombo p* (*; correspondence authors)and the working group: Alcaide P, Navarrete R, Sanz P, Font-Llitjós M, Vilaseca MA, Ormaizabal A, Pristoupilova A, Agulló SB . Hum Mutat . 2014 Apr;35(4):470-7 . doi: 10 .1002/humu .22513 . Epub 2014 Mar 5 .PMID: 24449431
• Cerebral cortex hyperthyroidism of newborn mct8-deficient mice transiently suppressed by lat2 inactivation . núñez b, martínez De mena r, obreGon mJ, Font-llitJós m, nunes V, palacín m, Dumitrescu am, morte b, ber- nal J.PLoS One . 2014 May 12;9(5):e96915 . doi: 10 .1371/journal .pone .0096915 . eCollection 2014 .PMID: 24819605 [PubMed - indexed for MEDLINE] Free PMC Article
• Autophagy-regulating TP53INP2 mediates muscle wasting and is repressed in diabetes . sala D, iVanoVa s, pla- na n, ribas V, Durán J, bacH D, turKseVen s, laVille m, ViDal H, KarczeWsKa-KupczeWsKa m, KoWalsKa i, straczKoWsKi m, testar x, palacín m, sanDri m, serrano al, zorzano a. J Clin Invest . 2014 May;124(5):1914-27 . doi: 10 .1172/ JCI72327 . Epub 2014 Apr 8 .PMID: 24713655 [PubMed - indexed for MEDLINE] Free PMC Article
Highlights
Institution: Fundación privada Instituto de Recerca Biomédica (IRB-Barcelona) Contact: Institut de Recerca en Biomedicina (IRB Barcelona) · Josep Samitier, 1-5 . 08028 Barcelona Tel .: (+34) 93 403 71 98/9 · E .mail: manuel .palacin@irbbarcelona .org · Website: www .irbbarcelona .org
We had generated and validated the first structural model at low resolution of a Heteromeric Amino acid Transporter (HAT), the human 4F2hc/LAT2 (publications 1 and 2) . This model offers the first structural clues for the molecular recognition and stabilization of the light subunit (LAT2) by the heavy subunit (4F2hc) . This model should also apply for HAT involved on rare diseases like lysinuric protein intolerance (4F2hc/y+LAT1) and cystinurias (rBAT/b0,+AT) (Fotiadis, Kanai y Palacín . Mol Aspects Med . 34:139-58, 2013) .
In collaboration with a group of CIBERER units (U703, U715, U730 y U746) we had studied the activity associated to mutations causing BCKDK deficiency (publication 3) and with units U708 y U730 we performed the phenotyping of the double KO for the thyroid hormone transporters MCT8 and LAT2 (Publication 4) . BCKDK deficit causes a form of inherited autism (Novarino et al . Science 338:394–397, 2012) .In our work we did identify new BCKDK mutations that add epilepsy and neural developmental defects to the syndrome . Our unit U731 expressed and purifies to homogeneity for the first time human BCKDK, which allowed a direct determination of the intrinsic activity of BCKDK mutants and demonstrated loss-of-function of the identified mutations .
Mutations in MCT8 cause Allan-Herndon-Dudley syndrome, but MCT8 KO do not phenocopy the syndrome in mice, suggesting compensation by other thyroid hormone transporters . Because 4F2hc/LAT2 is also a thyroid hormone transporter the double KO for MCT8 and LAT2 was generated . These mice did not developed Allan- Herndon-Dudley syndrome but uncover an early postnatal role of 4F2hc/LAT2 in the supply of thyroid hormones to cerebral cortex .
Finally, in collaboration with Prof . Antonio Zorzano lab (CIBERDEM) we had demonstrated the role of TP53INP2- modulated autophagy on skeletal muscle wasting in type 2 diabetes (publication 5) . This mechanism might be operative in other conditions with defective insulin action .
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