[Intracellular Mechanism of Gastric Acid Secretion: What is the True Switch?]
Yakugaku Zasshi
; 144(1): 99-117, 2024.
Article
en Ja
| MEDLINE
| ID: mdl-38171801
ABSTRACT
In 1985, I was accepted as postdoc by Professor Forte of UC Berkeley. He discovered H+,K+-ATPase and established the membrane recycling theory as the activation mechanism for acid secretion using whole animals. H+,K+-ATPase is an enzyme that exchanges H+ with K+. In resting state, it locates on the tubulovesicles and the pump does not work because the membrane lacks K+ permeability. Upon stimulation, the tubulovesicles fuse to the apical membrane and acquire K+ permeability, turning the pump on. The main route was known to be protein kinase A (PKA), but its specific targets remained unknown. Right after I joined Forte's lab, I was fortunate enough to reproduce the above mechanism in vitro, and I discovered proteins of molecular weight 120 kDa and 80 kDa that were specifically phosphorylated in stimulated parietal cells. After I returned to Japan, the former was cloned and named as parchorin, which is one of the chloride intracellular channels. Although no progress was made on ezrin, I found out the importance of PIP2 and Arf6 using permeabilized gland models. After I left parietal cell research, the link between ezrin and Arf6 was revealed. PKA phosphorylates S66 of ezrin and also MST4. The former changes the N-terminal structure of ezrin to bind syntaxin3, and the latter phosphorylates ACAP4, an Arf6-GAP, to accelerate binding to ezrin. Subsequently, H+,K+-ATPase, SNAREs, ezrin, and Arf6-GAP are aligned on the apical membrane. However, there are still many unsolved questions and the intracellular mechanism of parietal cells remains an attractive research area.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Parietales Gástricas
/
Ácido Gástrico
Límite:
Animals
Idioma:
Ja
Revista:
Yakugaku Zasshi
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Japón