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Endosidin2 targets conserved exocyst complex subunit EXO70 to inhibit exocytosis

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
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  1. Univ. of California, Riverside, CA (United States). Center for Plant Cell Biology. Inst. for Integrative Genome Biology. Dept. of Botany and Plant Sciences; DOE Office of Scientific and Technical Information (OSTI)
  2. Univ. of California, Riverside, CA (United States). Center for Plant Cell Biology. Inst. for Integrative Genome Biology. Dept. of Botany and Plant Sciences
  3. Univ. of California, Riverside, CA (United States). Dept. of Biochemistry
  4. Univ. of Pennsylvania, Philadelphia, PA (United States). Dept. of Biology
  5. Univ. of California, Riverside, CA (United States). Dept. of Chemistry
  6. Academy of Sciences of the Czech Republic (ASCR), Prague (Czech Republic). Inst. of Experimental Botany
  7. Univ. of California, Riverside, CA (United States). Dept. of Bioengineering
  8. Wake Forest Univ., Winston-Salem, NC (United States). Dept. of Biology. Center for Molecular Communication and Signaling
  9. Academy of Sciences of the Czech Republic (ASCR), Prague (Czech Republic). Inst. of Experimental Botany; Charles Univ., Prague (Czech Republic). Dept. of Experimental Plant Biology
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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. Ultimately, 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.
Research Organization:
Academy of Sciences of the Czech Republic (ASCR), Prague (Czech Republic); Univ. of California, Riverside, CA (United States); Wake Forest Univ., Winston-Salem, NC (United States)
Sponsoring Organization:
Czech Science Foundation (Czech Republic); National Aeronautics and Space Administration (NASA) (United States); USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Contributing Organization:
Charles Univ., Prague (Czech Republic); Univ. of Pennsylvania, Philadelphia, PA (United States)
Grant/Contract Number:
FG02-02ER15295
OSTI ID:
1348366
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 1 Vol. 113; ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)Copyright Statement
Country of Publication:
United States
Language:
English

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Expression and Functional Analysis of a Novel Group of Legume-specific WRKY and Exo70 Protein Variants from Soybean journal August 2016
Small molecules that inhibit the late stage of Munc13-4–dependent secretory granule exocytosis in mast cells journal May 2018
The Exocyst Complex in Health and Disease journal April 2016
Once for All: A Novel Robust System for Co-expression of Multiple Chimeric Fluorescent Fusion Proteins in Plants journal June 2017
Unconventional Transport Routes of Soluble and Membrane Proteins and Their Role in Developmental Biology journal March 2017
Tools of the Ethylene Trade: A Chemical Kit to Influence Ethylene Responses in Plants and Its Use in Agriculture journal August 2019
Disruption of endocytosis through chemical inhibition of clathrin heavy chain function journal April 2019
Understanding the language of drugged plants journal October 2019
Cryo-EM structure of the exocyst complex journal January 2018
Crystal structure of Sec10, a subunit of the exocyst complex journal January 2017
CSI1, PATROL1, and exocyst complex cooperate in delivery of cellulose synthase complexes to the plasma membrane journal March 2018
Casein kinase 1 family regulates PRR5 and TOC1 in the Arabidopsis circadian clock journal May 2019
Interaction between VPS35 and RABG3f is necessary as a checkpoint to control fusion of late compartments with the vacuole journal September 2019
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A broadly conserved NERD genetically interacts with the exocyst to affect root growth and cell expansion journal May 2018
Emerging strategies for the identification of protein–metabolite interactions journal May 2019
Three subfamilies of exocyst EXO70 family subunits in land plants: early divergence and ongoing functional specialization journal October 2019
Phosphorylation of the exocyst subunit Exo70B2 contributes to the regulation of its function posted_content January 2019
A Synthetic Peptide Encoded by a Random DNA Sequence Inhibits Discrete Red Light Responses posted_content June 2019
Osteoblastic lysosome plays a central role in mineralization journal July 2019
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Related Subjects

60 APPLIED LIFE SCIENCES
EXO70
endosidin2
exocyst
exocytosis