Lysine 204 is crucial for the antiport function of the human LAT1 transporter.

Amino acids Antiport Liposomes Molecular dynamics SLC Uniport

Journal

Biochimica et biophysica acta. Bioenergetics
ISSN: 1879-2650
Titre abrégé: Biochim Biophys Acta Bioenerg
Pays: Netherlands
ID NLM: 101731706

Informations de publication

Date de publication:
18 Oct 2024
Historique:
received: 15 05 2024
revised: 11 07 2024
accepted: 15 10 2024
medline: 21 10 2024
pubmed: 21 10 2024
entrez: 20 10 2024
Statut: aheadofprint

Résumé

LAT1 (SLC7A5) catalyzes an antiport reaction of amino acids with specificity towards the essential ones. It is mainly expressed at the Blood Brain Barrier and placenta barriers, but it becomes over-expressed in virtually all human cancers even if originating from tissues with lower expression levels. The antiport reaction of LAT1 is crucial at the BBB since its inherited loss causes Autism Spectrum Disorder. We have investigated the possible molecular determinant of the antiport by site-directed mutagenesis, in vitro transport assay and computational analysis. Previous data indicated that mutation of K204 impairs, but does not knock out LAT1 functionality. We have investigated the activity changes in the K204Q mutant by following the transport of [

Identifiants

pubmed: 39428051
pii: S0005-2728(24)00490-0
doi: 10.1016/j.bbabio.2024.149520
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

149520

Informations de copyright

Copyright © 2024. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Mariafrancesca Scalise (M)

Department DiBEST (Biologia, Ecologia, Scienze della Terra) Unit of Biochemistry and Molecular Biotechnology, University of Calabria, Via P. Bucci 4C, 87036 Arcavacata di Rende, Italy.

Raffaella Scanga (R)

Department DiBEST (Biologia, Ecologia, Scienze della Terra) Unit of Biochemistry and Molecular Biotechnology, University of Calabria, Via P. Bucci 4C, 87036 Arcavacata di Rende, Italy.

Lara Console (L)

Department DiBEST (Biologia, Ecologia, Scienze della Terra) Unit of Biochemistry and Molecular Biotechnology, University of Calabria, Via P. Bucci 4C, 87036 Arcavacata di Rende, Italy.

Michele Galluccio (M)

Department DiBEST (Biologia, Ecologia, Scienze della Terra) Unit of Biochemistry and Molecular Biotechnology, University of Calabria, Via P. Bucci 4C, 87036 Arcavacata di Rende, Italy.

Lorena Pochini (L)

Department DiBEST (Biologia, Ecologia, Scienze della Terra) Unit of Biochemistry and Molecular Biotechnology, University of Calabria, Via P. Bucci 4C, 87036 Arcavacata di Rende, Italy; CNR Institute of Biomembranes, Bioenergetics and Molecular Biotechnology, via Amendola 165/A, 70126 Bari, Italy. Electronic address: lorena.pochini@unical.it.

Cesare Indiveri (C)

Department DiBEST (Biologia, Ecologia, Scienze della Terra) Unit of Biochemistry and Molecular Biotechnology, University of Calabria, Via P. Bucci 4C, 87036 Arcavacata di Rende, Italy; CNR Institute of Biomembranes, Bioenergetics and Molecular Biotechnology, via Amendola 165/A, 70126 Bari, Italy. Electronic address: cesare.indiveri@unical.it.

Classifications MeSH