Syntaxin 1A is expressed in airway epithelial cells, where it modulates CFTR Cl(-) currents.
The CFTR Cl(-) channel controls salt and water transport across epithelial tissues. Previously, we showed that CFTR-mediated Cl(-) currents in the Xenopus oocyte expression system are inhibited by syntaxin 1A, a component of the membrane trafficking machinery. This negative modulation of CFTR function can be reversed by soluble syntaxin 1A peptides and by the syntaxin 1A binding protein, Munc-18. In the present study, we determined whether syntaxin 1A is expressed in native epithelial tissues that normally express CFTR and whether it modulates CFTR currents in these tissues. Using immunoblotting and immunofluorescence, we observed syntaxin 1A in native gut and airway epithelial tissues and showed that epithelial cells from these tissues express syntaxin 1A at >10-fold molar excess over CFTR. Syntaxin 1A is seen near the apical cell surfaces of human bronchial airway epithelium. Reagents that disrupt the CFTR-syntaxin 1A interaction, including soluble syntaxin 1A cytosolic domain and recombinant Munc-18, augmented cAMP-dependent CFTR Cl(-) currents by more than 2- to 4-fold in mouse tracheal epithelial cells and cells derived from human nasal polyps, but these reagents did not affect CaMK II-activated Cl(-) currents in these cells.
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Gregory Fleming James Cystic Fibrosis Center and Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Di
A
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Cormet-Boyaka
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E
Boyaka
P N
PN
McGhee
J R
JR
Zhou
W
W
Akagawa
K
K
Fujiwara
T
T
Thome
U
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Engelhardt
J F
JF
Nelson
D J
DJ
Kirk
K L
KL
D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D017136:Ion Transport; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D012137:Respiratory System / Q000378:metabolism*; D050827:Syntaxin 1; D014981:Xenopus
D000954:Antigens, Surface; C505032:CFTR protein, human; D018118:Chloride Channels; D009419:Nerve Tissue Proteins; C494212:STX1A protein, human; C494214:Stx1a protein, mouse; D050827:Syntaxin 1; D019005:Cystic Fibrosis Transmembrane Conductance Regulator