Details

Autor(en) / Beteiligte

• Kurtyka, Magdalena
• Wessely, Frank
• Bau, Sarah
• Ifie, Eseoghene
• He, Liqun
• de Wit, Nienke M.
• Pedersen, Alberte Bay Villekjær
• Keller, Maximilian
• Webber, Caleb
• de Vries, Helga E.
• Ansorge, Olaf
• Betsholtz, Christer
• De Bock, Marijke
• Chaves, Catarina
• Brodin, Birger
• Nielsen, Morten S.
• Neuhaus, Winfried
• Bell, Robert D.
• Letoha, Tamás
• Meyer, Axel H.
• Leparc, Germán
• Lenter, Martin
• Lesuisse, Dominique
• Cader, Zameel M.
• Buckley, Stephen T.
• Loryan, Irena
• Pietrzik, Claus U.

Titel

The solute carrier SLC7A1 may act as a protein transporter at the blood-brain barrier

Ist Teil von

• European journal of cell biology, 2024-06, Vol.103 (2), p.151406-151406, Article 151406

Ort / Verlag

Germany: Elsevier GmbH

Erscheinungsjahr

2024

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• Despite extensive research, targeted delivery of substances to the brain still poses a great challenge due to the selectivity of the blood-brain barrier (BBB). Most molecules require either carrier- or receptor-mediated transport systems to reach the central nervous system (CNS). These transport systems form attractive routes for the delivery of therapeutics into the CNS, yet the number of known brain endothelium-enriched receptors allowing the transport of large molecules into the brain is scarce. Therefore, to identify novel BBB targets, we combined transcriptomic analysis of human and murine brain endothelium and performed a complex screening of BBB-enriched genes according to established selection criteria. As a result, we propose the high-affinity cationic amino acid transporter 1 (SLC7A1) as a novel candidate for transport of large molecules across the BBB. Using RNA sequencing and in situ hybridization assays, we demonstrated elevated SLC7A1 gene expression in both human and mouse brain endothelium. Moreover, we confirmed SLC7A1 protein expression in brain vasculature of both young and aged mice. To assess the potential of SLC7A1 as a transporter for larger proteins, we performed internalization and transcytosis studies using a radiolabelled or fluorophore-labelled anti-SLC7A1 antibody. Our results showed that SLC7A1 internalised a SLC7A1-specific antibody in human colorectal carcinoma (HCT116) cells. Moreover, transcytosis studies in both immortalised human brain endothelial (hCMEC/D3) cells and primary mouse brain endothelial cells clearly demonstrated that SLC7A1 effectively transported the SLC7A1-specific antibody from luminal to abluminal side. Therefore, here in this study, we present for the first time the SLC7A1 as a novel candidate for transport of larger molecules across the BBB. •Cationic amino acid transporter 1 gene SLC7A1 is enriched in the brain endothelium.•SLC7A1 transporter is able to transcytose antibodies in the immortalized human brain endothelial cell line (hCMEC/D3).•SLC7A1 transporter at the BBB effectively transports antibodies across primary mouse brain endothelial cells in vitro.•SLC7A1 may be a potential candidate to transport substances across the BBB.