TY - JOUR
T1 - Sortin1-hypersensitive mutants link vacuolar-trafficking defects and flavonoid metabolism in Arabidopsis vegetative tissues
AU - Rosado, Abel
AU - Hicks, Glenn R.
AU - Norambuena, Lorena
AU - Rogachev, Ilana
AU - Meir, Sagit
AU - Pourcel, Lucille
AU - Zouhar, Jan
AU - Brown, Michelle Q.
AU - Boirsdore, Marietta P.
AU - Puckrin, Rachel S.
AU - Cutler, Sean R.
AU - Rojo, Enrique
AU - Aharoni, Asaph
AU - Raikhel, Natasha V.
N1 - NSF [MCB-0515963]; DOE/BES [DE-FG02-02ER15295]; Postdoctoral Fulbright Fellowship Award [FU-2006-0248]We would like to thank Dr. G. Di Sansebastiano (Universita di Lecce), Dr. M. Grebe (Umea University), and Dr. G. Drakakaki (University of California, Davis) for their donation of the GFP: KDEL, GFP: NAG1, and CFP: SYP61 marker lines, respectively, Dr. E. Grotewold (Ohio State University) for helpful discussions, and Dr. W. van de Ven and L. Johnson for technical assistance. The Sortin1 work was supported by the NSF (MCB-0515963 to N.V.R.) and the mtv6 mutant work by the DOE/BES Physical Biosciences program (DE-FG02-02ER15295 to N.V.R.) and by a Postdoctoral Fulbright Fellowship Award (FU-2006-0248 to A.R.).
PY - 2011/2/25
Y1 - 2011/2/25
N2 - Sortin1 is a chemical genetic-hit molecule that causes specific mislocalization of plant and yeast-soluble and membrane vacuolar markers. To better understand its mode of action, we designed a Sortin1-hypersensitive screen and identified several Sortin1-hypersensitive and flavonoid-defective mutants. Mechanistically, Sortin1 mimics the effect of the glutathione inhibitor buthionine sulfoximine and alters the vacuolar accumulation of flavonoids, likely blocking their transport through vacuole-localized ABC transporters. Structure-activity relationship studies conducted in Arabidopsis revealed the structural requirements for Sortin1 bioactivity and demonstrated that overlapping Sortin1 substructures can be used to discriminate between vacuolar-flavonoid accumulations and vacuolar-biogenesis defects. We conclude that Sortin1 is a valuable probe for dissecting novel links among flavonoid transport, vacuolar integrity, and the trafficking of vacuolar targeted cargoes in Arabidopsis.
AB - Sortin1 is a chemical genetic-hit molecule that causes specific mislocalization of plant and yeast-soluble and membrane vacuolar markers. To better understand its mode of action, we designed a Sortin1-hypersensitive screen and identified several Sortin1-hypersensitive and flavonoid-defective mutants. Mechanistically, Sortin1 mimics the effect of the glutathione inhibitor buthionine sulfoximine and alters the vacuolar accumulation of flavonoids, likely blocking their transport through vacuole-localized ABC transporters. Structure-activity relationship studies conducted in Arabidopsis revealed the structural requirements for Sortin1 bioactivity and demonstrated that overlapping Sortin1 substructures can be used to discriminate between vacuolar-flavonoid accumulations and vacuolar-biogenesis defects. We conclude that Sortin1 is a valuable probe for dissecting novel links among flavonoid transport, vacuolar integrity, and the trafficking of vacuolar targeted cargoes in Arabidopsis.
UR - http://www.scopus.com/inward/record.url?scp=79951829297&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.chembiol.2010.11.015
DO - https://doi.org/10.1016/j.chembiol.2010.11.015
M3 - مقالة
SN - 1074-5521
VL - 18
SP - 187
EP - 197
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 2
ER -