Sorting Tubules Regulate Blood-Brain Barrier Transcytosis
Transcytosis across the blood-brain barrier (BBB) regulates key processes of the brain, but the intracellular sorting mechanisms that determine successful receptor-mediated transcytosis in brain endothelial cells (BECs) remain unidentified. Here, we used Transferrin receptor-based Brain Shuttle cons...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-12-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717317072 |
| _version_ | 1818622127394258944 |
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| author | Roberto Villaseñor Michael Schilling Janani Sundaresan Yves Lutz Ludovic Collin |
| author_facet | Roberto Villaseñor Michael Schilling Janani Sundaresan Yves Lutz Ludovic Collin |
| author_sort | Roberto Villaseñor |
| collection | DOAJ |
| description | Transcytosis across the blood-brain barrier (BBB) regulates key processes of the brain, but the intracellular sorting mechanisms that determine successful receptor-mediated transcytosis in brain endothelial cells (BECs) remain unidentified. Here, we used Transferrin receptor-based Brain Shuttle constructs to investigate intracellular transport in BECs, and we uncovered a pathway for the regulation of receptor-mediated transcytosis. By combining live-cell imaging and mathematical modeling in vitro with super-resolution microscopy of the BBB, we show that intracellular tubules promote transcytosis across the BBB. A monovalent construct (sFab) sorted for transcytosis was localized to intracellular tubules, whereas a bivalent construct (dFab) sorted for degradation formed clusters with impaired transport along tubules. Manipulating tubule biogenesis by overexpressing the small GTPase Rab17 increased dFab transport into tubules and induced its transcytosis in BECs. We propose that sorting tubules regulate transcytosis in BECs and may be a general mechanism for receptor-mediated transport across the BBB. |
| first_indexed | 2024-12-16T18:20:14Z |
| format | Article |
| id | doaj.art-00a494ec689c41c5a236252d412d480a |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-16T18:20:14Z |
| publishDate | 2017-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-00a494ec689c41c5a236252d412d480a2022-12-21T22:21:35ZengElsevierCell Reports2211-12472017-12-0121113256327010.1016/j.celrep.2017.11.055Sorting Tubules Regulate Blood-Brain Barrier TranscytosisRoberto Villaseñor0Michael Schilling1Janani Sundaresan2Yves Lutz3Ludovic Collin4Roche Pharma Research and Early Development (pRED), Neuro-Immunology, Roche Innovation Center Basel, SwitzerlandRoche Pharma Research and Early Development (pRED), Neuro-Immunology, Roche Innovation Center Basel, SwitzerlandRoche Pharma Research and Early Development (pRED), Neuro-Immunology, Roche Innovation Center Basel, SwitzerlandImaging Centre, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch-Graffenstaden, FranceRoche Pharma Research and Early Development (pRED), Neuro-Immunology, Roche Innovation Center Basel, SwitzerlandTranscytosis across the blood-brain barrier (BBB) regulates key processes of the brain, but the intracellular sorting mechanisms that determine successful receptor-mediated transcytosis in brain endothelial cells (BECs) remain unidentified. Here, we used Transferrin receptor-based Brain Shuttle constructs to investigate intracellular transport in BECs, and we uncovered a pathway for the regulation of receptor-mediated transcytosis. By combining live-cell imaging and mathematical modeling in vitro with super-resolution microscopy of the BBB, we show that intracellular tubules promote transcytosis across the BBB. A monovalent construct (sFab) sorted for transcytosis was localized to intracellular tubules, whereas a bivalent construct (dFab) sorted for degradation formed clusters with impaired transport along tubules. Manipulating tubule biogenesis by overexpressing the small GTPase Rab17 increased dFab transport into tubules and induced its transcytosis in BECs. We propose that sorting tubules regulate transcytosis in BECs and may be a general mechanism for receptor-mediated transport across the BBB.http://www.sciencedirect.com/science/article/pii/S2211124717317072blood brain barrierbrain endothelial cellstranscytosissorting tubulessuper-resolution |
| spellingShingle | Roberto Villaseñor Michael Schilling Janani Sundaresan Yves Lutz Ludovic Collin Sorting Tubules Regulate Blood-Brain Barrier Transcytosis Cell Reports blood brain barrier brain endothelial cells transcytosis sorting tubules super-resolution |
| title | Sorting Tubules Regulate Blood-Brain Barrier Transcytosis |
| title_full | Sorting Tubules Regulate Blood-Brain Barrier Transcytosis |
| title_fullStr | Sorting Tubules Regulate Blood-Brain Barrier Transcytosis |
| title_full_unstemmed | Sorting Tubules Regulate Blood-Brain Barrier Transcytosis |
| title_short | Sorting Tubules Regulate Blood-Brain Barrier Transcytosis |
| title_sort | sorting tubules regulate blood brain barrier transcytosis |
| topic | blood brain barrier brain endothelial cells transcytosis sorting tubules super-resolution |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717317072 |
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