title: Endosidin2 targets conserved exocyst complex subunit EXO70 to inhibit exocytosis.
abstract: 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.
authors.affiliation: Center for Plant Cell Biology, Institute for Integrative Genome Biology, University of California, Riverside, CA 92521; Department of Botany and Plant Sciences, University of California, Riverside, CA 92521;
authors.forename: Chunhua
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Center for Plant Cell Biology, Institute for Integrative Genome Biology, University of California, Riverside, CA 92521; Department of Botany and Plant Sciences, University of California, Riverside, CA 92521;
authors.forename: Michelle Q
authors.initials: MQ
authors.lastname: Brown
authors.affiliation: Center for Plant Cell Biology, Institute for Integrative Genome Biology, University of California, Riverside, CA 92521; Department of Botany and Plant Sciences, University of California, Riverside, CA 92521;
authors.forename: Wilhelmina
authors.initials: W
authors.lastname: van de Ven
authors.affiliation: Department of Biochemistry, University of California, Riverside, CA 92521;
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Zhang
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Chemistry, University of California, Riverside, CA 92521;
authors.forename: Michael C
authors.initials: MC
authors.lastname: Young
authors.affiliation: Institute of Experimental Botany, Academy of Sciences, 165 02 Prague 6, Czech Republic;
authors.forename: Lukáš
authors.initials: L
authors.lastname: Synek
authors.affiliation: Department of Chemistry, University of California, Riverside, CA 92521;
authors.forename: Dan
authors.initials: D
authors.lastname: Borchardt
authors.affiliation: Department of Bioengineering, University of California, Riverside, CA, 92521;
authors.forename: Reed
authors.initials: R
authors.lastname: Harrison
authors.affiliation: Center for Plant Cell Biology, Institute for Integrative Genome Biology, University of California, Riverside, CA 92521; Department of Botany and Plant Sciences, University of California, Riverside, CA 92521;
authors.forename: Songqin
authors.initials: S
authors.lastname: Pan
authors.affiliation: Center for Plant Cell Biology, Institute for Integrative Genome Biology, University of California, Riverside, CA 92521; Department of Botany and Plant Sciences, University of California, Riverside, CA 92521;
authors.forename: Nan
authors.initials: N
authors.lastname: Luo
authors.affiliation: Department of Chemistry, University of California, Riverside, CA 92521;
authors.forename: Yu-Ming M
authors.initials: YM
authors.lastname: Huang
authors.affiliation: Department of Chemistry, University of California, Riverside, CA 92521;
authors.forename: Yoo-Jin
authors.initials: YJ
authors.lastname: Ghang
authors.affiliation: Center for Plant Cell Biology, Institute for Integrative Genome Biology, University of California, Riverside, CA 92521; Department of Botany and Plant Sciences, University of California, Riverside, CA 92521;
authors.forename: Nolan
authors.initials: N
authors.lastname: Ung
authors.affiliation: Center for Plant Cell Biology, Institute for Integrative Genome Biology, University of California, Riverside, CA 92521; Department of Botany and Plant Sciences, University of California, Riverside, CA 92521;
authors.forename: Ruixi
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Biology, Wake Forest University, Winston-Salem, NC 27109; Center for Molecular Communication and Signaling, Wake Forest University, Winston-Salem, NC 27109;
authors.forename: Jonathan
authors.initials: J
authors.lastname: Isley
authors.affiliation: Department of Bioengineering, University of California, Riverside, CA, 92521;
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Morikis
authors.affiliation: Department of Biochemistry, University of California, Riverside, CA 92521;
authors.forename: Jikui
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Chemistry, University of California, Riverside, CA 92521;
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Hooley
authors.affiliation: Department of Chemistry, University of California, Riverside, CA 92521;
authors.forename: Chia-En A
authors.initials: CE
authors.lastname: Chang
authors.affiliation: Center for Plant Cell Biology, Institute for Integrative Genome Biology, University of California, Riverside, CA 92521; Department of Botany and Plant Sciences, University of California, Riverside, CA 92521;
authors.forename: Zhenbiao
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Institute of Experimental Botany, Academy of Sciences, 165 02 Prague 6, Czech Republic; Department of Experimental Plant Biology, Faculty of Sciences, Charles University, 128 43 Prague 2, Czech Republic.
authors.forename: Viktor
authors.initials: V
authors.lastname: Zarsky
authors.affiliation: Department of Biology, Wake Forest University, Winston-Salem, NC 27109; Center for Molecular Communication and Signaling, Wake Forest University, Winston-Salem, NC 27109;
authors.forename: Gloria K
authors.initials: GK
authors.lastname: Muday
authors.affiliation: Center for Plant Cell Biology, Institute for Integrative Genome Biology, University of California, Riverside, CA 92521; Department of Botany and Plant Sciences, University of California, Riverside, CA 92521;
authors.forename: Glenn R
authors.initials: GR
authors.lastname: Hicks
authors.affiliation: Center for Plant Cell Biology, Institute for Integrative Genome Biology, University of California, Riverside, CA 92521; Department of Botany and Plant Sciences, University of California, Riverside, CA 92521; natasha.raikhel@ucr.edu.
authors.forename: Natasha V
authors.initials: NV
authors.lastname: Raikhel
mesh_terms: D017360:Arabidopsis / Q000378:metabolism*; D029681:Arabidopsis Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D017124:Conserved Sequence; D011992:Endosomes / Q000378:metabolism*; D019143:Evolution, Molecular; D005089:Exocytosis; D006801:Humans; D036701:Limonins / Q000378:metabolism*; D017433:Protein Structure, Secondary
chemical_list: D029681:Arabidopsis Proteins; C515561:EXO70A1 protein, Arabidopsis; D036701:Limonins; C000607936:endosidin 2
keywords: EXO70; endosidin2; exocyst; exocytosis