ABCC4 p.Leu1325Ala
| Predicted by SNAP2: | A: D (59%), C: N (61%), D: D (75%), E: D (71%), F: N (57%), G: D (71%), H: D (66%), I: N (78%), K: D (71%), M: N (82%), N: D (66%), P: D (75%), Q: D (59%), R: D (71%), S: D (63%), T: D (59%), V: N (87%), W: D (63%), Y: D (53%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, M: N, N: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: N, Y: N, |
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[hide] Spatiotemporal coupling of cAMP transporter to CFT... Cell. 2007 Nov 30;131(5):940-51. Li C, Krishnamurthy PC, Penmatsa H, Marrs KL, Wang XQ, Zaccolo M, Jalink K, Li M, Nelson DJ, Schuetz JD, Naren AP
Spatiotemporal coupling of cAMP transporter to CFTR chloride channel function in the gut epithelia.
Cell. 2007 Nov 30;131(5):940-51., [PMID:18045536]
Abstract [show]
Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated chloride channel localized at apical cell membranes and exists in macromolecular complexes with a variety of signaling and transporter molecules. Here, we report that the multidrug resistance protein 4 (MRP4), a cAMP transporter, functionally and physically associates with CFTR. Adenosine-stimulated CFTR-mediated chloride currents are potentiated by MRP4 inhibition, and this potentiation is directly coupled to attenuated cAMP efflux through the apical cAMP transporter. CFTR single-channel recordings and FRET-based intracellular cAMP dynamics suggest that a compartmentalized coupling of cAMP transporter and CFTR occurs via the PDZ scaffolding protein, PDZK1, forming a macromolecular complex at apical surfaces of gut epithelia. Disrupting this complex abrogates the functional coupling of cAMP transporter activity to CFTR function. Mrp4 knockout mice are more prone to CFTR-mediated secretory diarrhea. Our findings have important implications for disorders such as inflammatory bowel disease and secretory diarrhea.
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No. Sentence Comment
159 We synthesized various peptides, with and without a biotin conjugate at the N terminus (MRP4-C10 WT), and mutant peptides with the alanine substitution point mutation of the last amino acid within the tripeptide PDZ motif (MRP4-C10-L1325A) (Figure 7A) and the alanine substitution mutations of the whole tripeptide PDZ motif (MRP4-C10-AAA) (Figure S6A).
X
ABCC4 p.Leu1325Ala 18045536:159:232
status: NEW171 MRP4-L1325A mutant peptide behaved in a similar fashion to the biotin control (Figure S6B).
X
ABCC4 p.Leu1325Ala 18045536:171:5
status: NEW198 MRP4 Peptides that Disrupt MRP4 Interaction with PDZK1 Attenuate Elevation of CFTR ClÀ Currents Mediated by MRP4 Inhibition (A) PDZK1 binding to MRP4 in the presence of biotin-conjugated MRP4 C-tail peptides (last 10 amino acids; wild-type and mutant L1325A).
X
ABCC4 p.Leu1325Ala 18045536:198:251
status: NEW253 MRP4 Peptide In Vitro Competitive Binding MRP4 peptides (biotin-conjugated wild-type or L1325A mutant peptide, or nonconjugated wild-type or C10-AAA mutant peptide; 2 mM each) were mixed with His-PDZK1 (1.3 and 6.6 nM) at 22 C-24 C for 1 hr before GST-MRP4-C50 (immobilized on glutathione beads) was added; the solution was then mixed for another hour.
X
ABCC4 p.Leu1325Ala 18045536:253:88
status: NEW158 We synthesized various peptides, with and without a biotin conjugate at the N terminus (MRP4-C10 WT), and mutant peptides with the alanine substitution point mutation of the last amino acid within the tripeptide PDZ motif (MRP4-C10-L1325A) (Figure 7A) and the alanine substitution mutations of the whole tripeptide PDZ motif (MRP4-C10-AAA) (Figure S6A).
X
ABCC4 p.Leu1325Ala 18045536:158:232
status: NEW170 MRP4-L1325A mutant peptide behaved in a similar fashion to the biotin control (Figure S6B).
X
ABCC4 p.Leu1325Ala 18045536:170:5
status: NEW197 MRP4 Peptides that Disrupt MRP4 Interaction with PDZK1 Attenuate Elevation of CFTR Cl Currents Mediated by MRP4 Inhibition (A) PDZK1 binding to MRP4 in the presence of biotin-conjugated MRP4 C-tail peptides (last 10 amino acids; wild-type and mutant L1325A).
X
ABCC4 p.Leu1325Ala 18045536:197:251
status: NEW252 MRP4 Peptide In Vitro Competitive Binding MRP4 peptides (biotin-conjugated wild-type or L1325A mutant peptide, or nonconjugated wild-type or C10-AAA mutant peptide; 2 mM each) were mixed with His-PDZK1 (1.3 and 6.6 nM) at 22 C-24 C for 1 hr before GST-MRP4-C50 (immobilized on glutathione beads) was added; the solution was then mixed for another hour.
X
ABCC4 p.Leu1325Ala 18045536:252:88
status: NEW