Endosidin2 targets conserved exocyst complex subunit EXO70 to inhibit exocytosis

0456183 - ÚEB 2016 RIV US eng J - Journal Article
Zhang, C. - Brown, M.Q. - van de Ven, W. - Zhang, Z.M. - Wu, B. - Young, M.C. - Synek, Lukáš - Borchardt, D. - Harrison, R. - Pan, S.Q. - Luo, N. - Huang, Y.M.M. - Ghang, Y.J. - Ung, N. - Li, R.X. - Isley, J. - Morikis, D. - Song, J.K. - Guo, W. - Hooley, R.J. - Chang, C.E.A. - Yang, Z.B. - Žárský, Viktor - Muday, G.K. - Hicks, G.R. - Raikhel, N.V.
Endosidin2 targets conserved exocyst complex subunit EXO70 to inhibit exocytosis.
Proceedings of the National Academy of Sciences of the United States of America. Roč. 113, č. 1 (2016), E41-E50. ISSN 0027-8424. E-ISSN 1091-6490
R&D Projects: GA ČR(CZ) GA15-14886S
Institutional support: RVO:61389030
Keywords : endosidin2 * exocytosis * exocyst
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 9.661, year: 2016

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.
Permanent Link: http://hdl.handle.net/11104/0256759