Author, as appears in the article.: Knopfel, Emilia Boiadjieva; Vilches, Clara; Camargo, Simone M R; Errasti-Murugarren, Ekaitz; Staubli, Andrina; Mayayo, Clara; Munier, Francis L; Miroshnikova, Nataliya; Poncet, Nadege; Junza, Alexandra; Bhattacharya, Shomi S; Prat, Esther; Berry, Vanita; Berger, Wolfgang; Heon, Elise; Moore, Anthony T; Yanes, Oscar; Nunes, Virginia; Palacin, Manuel; Verrey, Francois; Kloeckener-Gruissem, Barbara
Department: Enginyeria Electrònica, Elèctrica i Automàtica
URV's Author/s: Junza Martínez, Alexandra / Yanes Torrado, Óscar
Keywords: 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
Abstract: © 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.
Thematic Areas: 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
licence for use: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 1664042X
Author's mail: oscar.yanes@urv.cat alexandra.junza@urv.cat
Author identifier: 0000-0003-3695-7157 0000-0001-7205-0419
Record's date: 2024-10-12
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://www.frontiersin.org/articles/10.3389/fphys.2019.00688/full
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Frontiers In Physiology. 10 (JUN): 688-
APA: Knopfel, Emilia Boiadjieva; Vilches, Clara; Camargo, Simone M R; Errasti-Murugarren, Ekaitz; Staubli, Andrina; Mayayo, Clara; Munier, Francis L; Miros (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
Article's DOI: 10.3389/fphys.2019.00688
Entity: Universitat Rovira i Virgili
Journal publication year: 2019
Publication Type: Journal Publications
Repositori URV