Journal article
Bidirectional apical-basal traffic of the cation-independent mannose-6-phosphate receptor in brain endothelial cells
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.
Language: | English |
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Publisher: | SAGE Publications |
Year: | 2017 |
Pages: | 2598-2613 |
ISSN: | 15597016 and 0271678x |
Types: | Journal article |
DOI: | 10.1177/0271678X17700665 |
ORCIDs: | 0000-0002-6702-183X , 0000-0001-9863-9694 and Andresen, Thomas Lars |
Blood–brain barrier Brain endothelial cells Mannose-6-phosphate receptors Trafficking Transcytosis
Animals Astrocytes Blood-Brain Barrier Brain Capillaries Cattle Cells, Cultured Coculture Techniques Endothelial Cells Endothelium, Vascular Fibroblasts Humans Journal Article Mice Models, Biological Pharmaceutical Preparations Protein Transport Rats Receptor, IGF Type 2 Swine blood–brain barrier brain endothelial cells trafficking transcytosis