ABCB1 p.Tyr42Ala
| Predicted by SNAP2: | A: D (75%), C: D (59%), D: D (85%), E: D (91%), F: N (93%), G: D (85%), H: D (71%), I: D (80%), K: D (91%), L: D (75%), M: D (85%), N: D (85%), P: D (91%), Q: D (85%), R: D (91%), S: D (85%), T: D (80%), V: D (75%), W: D (80%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: N, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, |
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[hide] P-glycoprotein in blood-brain barrier endothelial ... J Neurochem. 2003 Nov;87(4):1010-23. Jodoin J, Demeule M, Fenart L, Cecchelli R, Farmer S, Linton KJ, Higgins CF, Beliveau R
P-glycoprotein in blood-brain barrier endothelial cells: interaction and oligomerization with caveolins.
J Neurochem. 2003 Nov;87(4):1010-23., [PMID:14622130]
Abstract [show]
P-glycoprotein (P-gp), an adenosine triphosphate (ATP)-binding cassette transporter which acts as a drug efflux pump, is highly expressed at the blood-brain barrier (BBB) where it plays an important role in brain protection. Recently, P-gp has been reported to be located in the caveolae of multidrug-resistant cells. In this study, we investigated the localization and the activity of P-gp in the caveolae of endothelial cells of the BBB. We used an in vitro model of the BBB which is formed by co-culture of bovine brain capillary endothelial cells (BBCEC) with astrocytes. Caveolar microdomains isolated from BBCEC are enriched in P-gp, cholesterol, caveolin-1, and caveolin-2. Moreover, P-gp interacts with caveolin-1 and caveolin-2; together, they form a high molecular mass complex. P-gp in isolated caveolae is able to bind its substrates, and the caveolae-disrupting agents filipin III and nystatin decrease P-gp transport activity. In addition, mutations in the caveolin-binding motif present in P-gp reduced the interaction of P-gp with caveolin-1 and increased the transport activity of P-gp. Thus, P-gp expressed at the BBB is mainly localized in caveolae and its activity may be modulated by interaction with caveolin-1.
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No. Sentence Comment
75 The MDR1 codons for Tyr42 and Trp45 were replaced with Ala codons by Quikchange protocol (Stratagene, La Jolla, CA, USA) using the primer 5'-TCAATGTTTCGCGCTTCGAATGCGCTTGACAAGT- TG-3' and a primer with the reverse complement sequence.
X
ABCB1 p.Tyr42Ala 14622130:75:20
status: NEW207 In the first P-gp mutant, Tyr42 and Trp45 were replaced with Ala residues (YWAA-MDR1).
X
ABCB1 p.Tyr42Ala 14622130:207:26
status: NEW