RT Journal Article
T1 Dysfunctional LAT2 Amino Acid Transporter Is Associated With Cataract in Mouse and Humans.
A1 Knöpfel, Emilia Boiadjieva
A1 Vilches, Clara
A1 Camargo, Simone M R
A1 Errasti-Murugarren, Ekaitz
A1 Stäubli, Andrina
A1 Mayayo, Clara
A1 Munier, Francis L
A1 Miroshnikova, Nataliya
A1 Poncet, Nadège
A1 Junza, Alexandra
A1 Bhattacharya, Shomi S
A1 Prat, Esther
A1 Berry, Vanita
A1 Berger, Wolfgang
A1 Heon, Elise
A1 Moore, Anthony T
A1 Yanes, Óscar
A1 Nunes, Virginia
A1 Palacín, Manuel
A1 Verrey, Francois
A1 Kloeckener-Gruissem, Barbara
K1 amino acid transporters LAT2 and TAT1
K1 cataract
K1 gene expression
K1 mouse model
K1 ocular tissues
K1 patient screen
AB 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.
SN 1664-042X
YR 2019
FD 2019-06-04
LK http://hdl.handle.net/10668/14161
UL http://hdl.handle.net/10668/14161
LA en
DS RISalud
RD Apr 11, 2025