Identification of cellular pathways affected by Sortin2, a synthetic compound that affects protein targeting to the vacuole in Saccharomyces cerevisiae

BMC Chemical Biology
Lorena NorambuenaNatasha V Raikhel

Abstract

Sortin2 is a low mass compound that interferes with vacuolar delivery of proteins in plants and yeast. The Sortin2 phenotype was tested in Arabidopsis thaliana and found to be reversible upon drug removal, demonstrating the ability of chemical genomics to induce reversible phenotypes that would be difficult to achieve using conventional genetics 1. However, standard genetic methods can be used to identify drug target pathways in a high-throughput manner. In this study, we analyzed structure-function relationships of Sortin2 using structural analogues. The results show the key roles of sulphite substitution and a benzoic acid group. A Sortin 2 hypersensitivity screen for the induced secretion of a vacuolar cargo protein was done utilizing a yeast haploid deletion library. Using bioinformatics approaches, we highlighted functional information about the cellular pathways affected by drug treatment which included protein sorting and other endomembrane system-related processes. Chemical, genomic and genetics approaches were used to understand the mode of action of Sortin2, a bioactive chemical that affects the delivery of a vacuolar protein. Critical features of Sortin2 structure necessary for bioactivity suggest a binding pocket th...Continue Reading

References

Oct 23, 1974·Biochemical and Biophysical Research Communications·J F LenneyJ Meyer
Feb 11, 1982·Biochemical and Biophysical Research Communications·H SchwaigerW Tanner
Feb 21, 1998·Nucleic Acids Research·J M CherryD Botstein
Nov 15, 2000·Proceedings of the National Academy of Sciences of the United States of America·T F ChanX F Zheng
Apr 3, 2001·Proceedings of the National Academy of Sciences of the United States of America·T ItoY Sakaki
Jul 23, 2002·Molecular Biology of the Cell·Cecilia J BonangelinoJuan S Bonifacino
Jan 28, 2003·Current Opinion in Chemical Biology·R Scott Lokey
Oct 17, 2003·Nature·Won-Ki HuhErin K O'Shea
Jan 14, 2004·Proceedings of the National Academy of Sciences of the United States of America·Guri GiaeverRonald W Davis
Feb 7, 2004·Science·Amy Hin Yan TongCharles Boone
May 18, 2004·Proceedings of the National Academy of Sciences of the United States of America·Rebecca A Butcher, Stuart L Schreiber
May 27, 2004·Proceedings of the National Academy of Sciences of the United States of America·Syed H AskreeMichael J McEachern
Jun 11, 2004·Proceedings of the National Academy of Sciences of the United States of America·Jan ZouharNatasha V Raikhel
May 26, 2005·Biochimica Et Biophysica Acta·Katherine Bowers, Tom H Stevens
Jun 16, 2005·Plant Physiology·Thomas GirkeNatasha Raikhel
Jan 13, 2006·Nature Chemical Biology·Stuart L Schreiber
Dec 8, 2006·Molecular Biology of the Cell·Andrea J OestreichDavid J Katzmann

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Citations

Mar 13, 2012·Annual Review of Plant Biology·Glenn R Hicks, Natasha V Raikhel
Sep 21, 2010·Current Opinion in Plant Biology·Glenn R Hicks, Natasha V Raikhel
Jul 26, 2015·Biological Research·Beatriz Vásquez-SotoLorena Norambuena
Aug 26, 2009·Plant Signaling & Behavior·Georgia DrakakakiGlenn R Hicks
Apr 23, 2013·Chemistry & Biology·Kiril MishevEugenia Russinova
Sep 27, 2008·Proceedings of the National Academy of Sciences of the United States of America·Sigal Savaldi-GoldsteinJoanne Chory
Feb 23, 2017·Annual Review of Plant Biology·Lorena Norambuena, Ricardo Tejos
Jan 1, 2009·The Arabidopsis Book·Stéphanie RobertGlenn R Hicks

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Methods Mentioned

BETA
Dot-blot
dot blot
GTPases

Software Mentioned

GO Slim Mapper
FunCat
GO Term Finder
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