ABCB1 p.Trp45Ala
| Predicted by SNAP2: | A: N (87%), C: N (93%), D: N (72%), E: N (87%), F: N (87%), G: N (82%), H: N (82%), I: N (82%), K: N (93%), L: N (87%), M: N (87%), N: N (87%), P: N (87%), Q: N (93%), R: N (93%), S: N (93%), T: N (93%), V: N (87%), Y: N (87%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, 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, Y: D, |
[switch to compact view]
Comments [show]
None has been submitted yet.
[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.
Comments [show]
None has been submitted yet.
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.Trp45Ala 14622130:75:30
status: NEW207 In the first P-gp mutant, Tyr42 and Trp45 were replaced with Ala residues (YWAA-MDR1).
X
ABCB1 p.Trp45Ala 14622130:207:36
status: NEW