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Apicobasal transferrin receptor localization and trafficking in brain capillary endothelial cells.
Nielsen, Simone S E; Holst, Mikkel R; Langthaler, Kristine; Christensen, Sarah Christine; Bruun, Elisabeth Helena; Brodin, Birger; Nielsen, Morten S.
Afiliación
  • Nielsen SSE; Department of Biomedicine, Faculty of Health, Aarhus University, 8000, Aarhus C, Denmark.
  • Holst MR; Department of Biomedicine, Faculty of Health, Aarhus University, 8000, Aarhus C, Denmark.
  • Langthaler K; CNS Drug Delivery and Barrier Modelling, University of Copenhagen, Copenhagen, Denmark.
  • Christensen SC; Translational DMPK, H. Lundbeck A/S, Copenhagen, Denmark.
  • Bruun EH; Pathology & Imaging, Novo Nordisk, Måløv, Denmark.
  • Brodin B; Department of Biomedicine, Faculty of Health, Aarhus University, 8000, Aarhus C, Denmark.
  • Nielsen MS; Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, 2100, Copenhagen, Denmark.
Fluids Barriers CNS ; 20(1): 2, 2023 Jan 09.
Article en En | MEDLINE | ID: mdl-36624498
The detailed mechanisms by which the transferrin receptor (TfR) and associated ligands traffic across brain capillary endothelial cells (BECs) of the CNS-protective blood-brain barrier constitute an important knowledge gap within maintenance and regulation of brain iron homeostasis. This knowledge gap also presents a major obstacle in research aiming to develop strategies for efficient receptor-mediated drug delivery to the brain. While TfR-mediated trafficking from blood to brain have been widely studied, investigation of TfR-mediated trafficking from brain to blood has been limited. In this study we investigated TfR distribution on the apical and basal plasma membranes of BECs using expansion microscopy, enabling sufficient resolution to separate the cellular plasma membranes of these morphological flat cells, and verifying both apical and basal TfR membrane domain localization. Using immunofluorescence-based transcellular transport studies, we delineated endosomal sorting of TfR endocytosed from the apical and basal membrane, respectively, as well as bi-directional TfR transcellular transport capability. The findings indicate different intracellular sorting mechanisms of TfR, depending on the apicobasal trafficking direction across the BBB, with the highest transcytosis capacity in the brain-to-blood direction. These results are of high importance for the current understanding of brain iron homeostasis. Also, the high level of TfR trafficking from the basal to apical membrane of BECs potentially explains the low transcytosis which are observed for the TfR-targeted therapeutics to the brain parenchyma.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Células Endoteliales Idioma: En Revista: Fluids Barriers CNS Año: 2023 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Células Endoteliales Idioma: En Revista: Fluids Barriers CNS Año: 2023 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Reino Unido