Specific AHNAK expression in brain endothelial cells with barrier properties.
The blood-brain barrier (BBB) is essential for maintaining brain homeostasis and low permeability. Because disruption of the BBB may contribute to many brain disorders, they are of considerable interests in the identification of the molecular mechanisms of BBB development and integrity. We here report that the giant protein AHNAK is expressed at the plasma membrane of endothelial cells (ECs) forming specific blood-tissue barriers, but is absent from the endothelium of capillaries characterized by extensive molecular exchanges between blood and extracellular fluid. In the brain, AHNAK is widely distributed in ECs with BBB properties, where it co-localizes with the tight junction protein ZO-1. AHNAK is absent from the permeable brain ECs of the choroid plexus and is down-regulated in permeable angiogenic ECs of brain tumors. In the choroid plexus, AHNAK accumulates at the tight junctions of the choroid epithelial cells that form the blood-cerebrospinal fluid (CSF) barrier. In EC cultures, the regulation of AHNAK expression and its localization corresponds to general criteria of a protein involved in barrier organization. AHNAK is up-regulated by angiopoietin-1 (Ang-1), a morphogenic factor that regulates brain EC permeability. In bovine cerebral ECs co-cultured with glial cells, AHNAK relocates from the cytosol to the plasma membrane when endothelial cells acquire BBB properties. Our results identify AHNAK as a protein marker of endothelial cells with barrier properties.
Gentil
Benoît J
BJ
Laboratoire de Transduction du Signal INSERM EMI-0104, Grenoble, France.
Benaud
Christelle
C
Delphin
Christian
C
Remy
Chantal
C
Berezowski
Vincent
V
Cecchelli
Roméo
R
Feraud
Olivier
O
Vittet
Daniel
D
Baudier
Jacques
J
D042683:Angiopoietin-1 / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000648:ultrastructure; D001921:Brain / Q000098:blood supply*; D001932:Brain Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000648:ultrastructure; D002417:Cattle; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002831:Choroid Plexus / Q000378:metabolism / Q000648:ultrastructure; D018920:Coculture Techniques; D003600:Cytosol / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D019108:Tight Junctions / Q000378:metabolism / Q000648:ultrastructure; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D062826:Zonula Occludens-1 Protein
C489572:Ahnak protein, mouse; D042683:Angiopoietin-1; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D010750:Phosphoproteins; C569043:Tjp1 protein, mouse; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein