Sorting Tubules Regulate Blood-Brain Barrier Transcytosis.
Cell Rep
; 21(11): 3256-3270, 2017 Dec 12.
Article
en En
| MEDLINE
| ID: mdl-29241551
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Barrera Hematoencefálica
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Proteínas de Unión al GTP rab
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Estructuras Citoplasmáticas
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Células Endoteliales
Límite:
Animals
Idioma:
En
Revista:
Cell Rep
Año:
2017
Tipo del documento:
Article
País de afiliación:
Suiza