Autor según el artículo: Knöpfel E; Vilches C; Camargo S; Errasti-Murugarren E; Stäubli A; Mayayo C; Munier F; Miroshnikova N; Poncet N; Junza A; Bhattacharya S; Prat E; Berry V; Berger W; Heon E; Moore A; Yanes Ó; Nunes V; Palacín M; Verrey F; Kloeckener-Gruissem B

Departamento: Enginyeria Electrònica, Elèctrica i Automàtica

Autor/es de la URV: Junza Martínez, Alexandra / Yanes Torrado, Óscar

Palabras clave: Unclassified drug Tat1 protein Slc7a8 gene Senile cataract Risk factor Patient screen Ocular tissues Nonhuman Mouse model Mouse Male Major clinical study Lens epithelium Lat2 protein Human cell Human Gene mutation Gene expression Gene Female Essential amino acid Disease association Controlled study Congenital cataract Ciliary body epithelium Cataract Article Animal tissue Animal model Animal experiment Amino acid transporters lat2 and tat1 Amino acid transporter Amino acid transport ocular tissues mouse model gene expression cataract amino acid transporters lat2 and tat1

Resumen: © 2007 - 2019 Frontiers Media S.A. All Rights Reserved. Cataract, the loss of ocular lens transparency, accounts for ~50% of worldwide blindness and has been associated with water and solute transport dysfunction across lens cellular barriers. We show that neutral amino acid antiporter LAT2 (Slc7a8) and uniporter TAT1 (Slc16a10) are expressed on mouse ciliary epithelium and LAT2 also in lens epithelium. Correspondingly, deletion of LAT2 induced a dramatic decrease in lens essential amino acid levels that was modulated by TAT1 defect. Interestingly, the absence of LAT2 led to increased incidence of cataract in mice, in particular in older females, and a synergistic effect was observed with simultaneous lack of TAT1. Screening SLC7A8 in patients diagnosed with congenital or age-related cataract yielded one homozygous single nucleotide deletion segregating in a family with congenital cataract. Expressed in HeLa cells, this LAT2 mutation did not support amino acid uptake. Heterozygous LAT2 variants were also found in patients with cataract some of which showed a reduced transport function when expressed in HeLa cells. Whether heterozygous LAT2 variants may contribute to the pathology of cataract needs to be further investigated. Overall, our results suggest that defects of amino acid transporter LAT2 are implicated in cataract formation, a situation that may be aggravated by TAT1 defects.

Áreas temáticas: Zootecnia / recursos pesqueiros Saúde coletiva Química Psicología Physiology (medical) Physiology Odontología Nutrição Medicina veterinaria Medicina iii Medicina ii Medicina i Interdisciplinar Farmacia Ensino Engenharias iv Educação física Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciências agrárias i Ciência de alimentos Biotecnología Astronomia / física Administração pública e de empresas, ciências contábeis e turismo

Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/

ISSN: 1664042X

Direcció de correo del autor: alexandra.junza@urv.cat oscar.yanes@urv.cat

Identificador del autor: 0000-0001-7205-0419 0000-0003-3695-7157

Fecha de alta del registro: 2023-02-22

Versión del articulo depositado: info:eu-repo/semantics/publishedVersion

Enlace a la fuente original: https://www.frontiersin.org/articles/10.3389/fphys.2019.00688/full

URL Documento de licencia: http://repositori.urv.cat/ca/proteccio-de-dades/

Referencia al articulo segun fuente origial: Frontiers In Physiology. 10 (JUN): 688-

Referencia de l'ítem segons les normes APA: Knöpfel E; Vilches C; Camargo S; Errasti-Murugarren E; Stäubli A; Mayayo C; Munier F; Miroshnikova N; Poncet N; Junza A; Bhattacharya S; Prat E; Berry (2019). Dysfunctional LAT2 amino acid transporter is associated with cataract in mouse and humans. Frontiers In Physiology, 10(JUN), 688-. DOI: 10.3389/fphys.2019.00688

DOI del artículo: 10.3389/fphys.2019.00688

Entidad: Universitat Rovira i Virgili

Año de publicación de la revista: 2019

Tipo de publicación: Journal Publications