Reduction of SNAP25 in acid secretion defect of Foxl1-/- gastric parietal cells.
Foxl1 is a winged helix transcription factor expressed in the mesenchyme of the gastrointestinal tract. In the absence of Foxl1, parietal cells fail to secrete gastric acid in response to various secretagogue stimuli including cAMP. A marked decrease in H+,K(+)-ATPase expression was observed even though a substantial number of parietal cells still existed in Foxl1-deficient mice. Ultrastructural analysis suggested that the gastric acid secretion defect in Foxl1-deficient mice is mainly due to impairment in the fusion of cytoplasmic tubulovesicular structures to the apical canalicular plasma membrane. Among the molecules involved in the membrane fusion event, only SNAP25 showed a significant decrease in mRNA expression, which likely caused the impairment in acid secretion from parietal cells in Foxl1-deficient mice, with the reduction in H+,K(+)-ATPase expression contributing to additional effect.
Kato
Yasutaka
Y
Department of Biological Sciences, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Fukamachi
Hiroshi
H
Takano-Maruyama
Masumi
M
Aoe
Tomohiko
T
Murahashi
Yasuaki
Y
Horie
Syunji
S
Suzuki
Yasuo
Y
Saito
Yasushi
Y
Koseki
Haruhiko
H
Ohno
Hiroshi
H
D000818:Animals; D018723:Bethanechol / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000172:deficiency*; D051858:Forkhead Transcription Factors; D005744:Gastric Acid / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010295:Parietal Cells, Gastric / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010418:Pentagastrin / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25; D014157:Transcription Factors / Q000172:deficiency*
D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C099993:Foxl1 protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C494209:Snap25 protein, mouse; D050825:Synaptosomal-Associated Protein 25; D014157:Transcription Factors; D018723:Bethanechol; D003994:Bucladesine; D000254:Sodium-Potassium-Exchanging ATPase; D010418:Pentagastrin