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A drug-like molecule targets conserved EXO70 to inhibit exocytosis and promote vacuole trafficking

日期: 2015-11-06

金沙威尼斯欢乐娱人城2015年度秋季学期学术系列讲座之七暨金沙威尼斯欢乐娱人城现代农业讲座

题目:A drug-like molecule targets conserved EXO70 to inhibit exocytosis and promote vacuole trafficking

讲座人:Natasha Raikhel, Ph.D.

Director, Institute for Integrative Genome Biology

Botany & Plant Sciences Department

University of CA, Riverside, USA

时间:2015年11月6日,13:00-14:30

地点:金沙威尼斯欢乐娱人城二教107

联系人:邓兴旺(62766648;deng@pku.edu.cn)

The exocyst complex regulates the last steps of exocytosis, which is essential to organisms across kingdoms. In humans, its disfunction 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) transiently arrests the EXO70 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 and C-terminus of the protein. This study provides not only new insights into the novel features of the exocyst complex but also offers a potentially new target for drugs aimed at addressing human disease.

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