26607451 OR Endosidin2 targets conserved exocyst complex subunit EXO70 to inhibit exocytosis Dotaz Zobrazit nápovědu
The exocyst complex regulates the last steps of exocytosis, which is essential to organisms across kingdoms. In humans, its dysfunction is correlated with several significant diseases, such as diabetes and cancer progression. Investigation of the dynamic regulation of the evolutionarily conserved exocyst-related processes using mutants in genetically tractable organisms such as Arabidopsis thaliana is limited by the lethality or the severity of phenotypes. We discovered that the small molecule Endosidin2 (ES2) binds to the EXO70 (exocyst component of 70 kDa) subunit of the exocyst complex, resulting in inhibition of exocytosis and endosomal recycling in both plant and human cells and enhancement of plant vacuolar trafficking. An EXO70 protein with a C-terminal truncation results in dominant ES2 resistance, uncovering possible distinct regulatory roles for the N terminus of the protein. This study not only provides a valuable tool in studying exocytosis regulation but also offers a potentially new target for drugs aimed at addressing human disease.
- MeSH
- Arabidopsis metabolismus MeSH
- buněčná membrána metabolismus MeSH
- endozomy metabolismus MeSH
- exocytóza * MeSH
- konzervovaná sekvence MeSH
- lidé MeSH
- limoniny metabolismus MeSH
- molekulární evoluce MeSH
- proteiny huseníčku chemie genetika metabolismus MeSH
- sekundární struktura proteinů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH