Bidirectional apical-basal traffic of the cation-independent mannose-6-phosphate receptor in brain endothelial cells

Piotr Siupka, Maria N. S. Hersom, Karin Lykke-Hartmann, Kasper B. Johnsen, Louiza B. Thomsen, Thomas Lars Andresen, Torben Moos, N. Joan Abbott, Birger Brodin, Morten S. Nielsen

    Research output: Contribution to journalJournal articlepeer-review

    Abstract

    Brain capillary endothelium mediates the exchange of nutrients between blood and brain parenchyma. This barrier function of the brain capillaries also limits passage of pharmaceuticals from blood to brain, which hinders treatment of several neurological disorders. Receptor-mediated transport has been suggested as a potential pharmaceutical delivery route across the brain endothelium, e.g. reports have shown that the transferrin receptor (TfR) facilitates transcytosis of TfR antibodies, but it is not known whether this recycling receptor itself traffics from apical to basal membrane in the process. Here, we elucidate the endosomal trafficking of the retrograde transported cation-independent mannose-6-phosphate receptor (MPR300) in primary cultures of brain endothelial cells (BECs) of porcine and bovine origin. Receptor expression and localisation of MPR300 in the endo-lysosomal system and trafficking of internalised receptor are analysed. We also demonstrate that MPR300 can undergo bidirectional apical-basal trafficking in primary BECs in co-culture with astrocytes. This is, to our knowledge, the first detailed study of retrograde transported receptor trafficking in BECs, and the study demonstrates that MPR300 can be transported from the luminal to abluminal membrane and reverse. Such trafficking of MPR300 suggests that retrograde transported receptors in general may provide a mechanism for transport of pharmaceuticals into the brain.
    Original languageEnglish
    JournalJournal of Cerebral Blood Flow and Metabolism
    Volume37
    Issue number7
    Pages (from-to)2598-2613
    Number of pages16
    ISSN0271-678X
    DOIs
    Publication statusPublished - 2017

    Keywords

    • Mannose-6-phosphate receptors
    • Blood–brain barrier
    • Transcytosis
    • Brain endothelial cells
    • Trafficking

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