TY - JOUR
T1 - The power of chemical genomics to study the link between endomembrane system components and the gravitropic response
AU - Surpin, Marci
AU - Rojas-Pierce, Marcela
AU - Carter, Clay
AU - Hicks, Glenn R.
AU - Vasquez, Jacob
AU - Raikhel, Natasha V.
PY - 2005/3/29
Y1 - 2005/3/29
N2 - Chemical genomics is a powerful approach to dissect processes that may be intractable using conventional genetics because of gene lethality or redundancy. Recently, a link has been established between endomembrane trafficking and gravitropism. To understand this link, we screened a library of 10,000 diverse chemicals for compounds that affected the gravitropism of Arabidopsis seedlings positively or negatively. Sixty-nine of 219 compounds from the primary screen were retested, and 34 of these were confirmed to inhibit or enhance gravitropism. Four of the 34 compounds were found to cause aberrant endomembrane morphologies. The chemicals affected gravitropism and vacuole morphology in concert in a tissue-specific manner, underscoring the link between endomembranes and gravitropism. One of the chemicals (5403629) was structurally similar to the synthetic auxin 2,4-dichlorophenoxy acetate, whereas the other three chemicals were unique in their structures. An in vivo functional assay using the reporter β-glucuronidase under the auxin-inducible DR5 promoter confirmed that the unique compounds were not auxins. Interestingly, one of the unique chemicals (5850247) appeared to decrease the responsiveness to auxin in roots, whereas another (5271050) was similar to pyocyanin, a bacterial metabolite that has been suggested to target the endomembranes of yeast. These reagents will be valuable for dissecting endomembrane trafficking and gravitropism and for cognate target identification.
AB - Chemical genomics is a powerful approach to dissect processes that may be intractable using conventional genetics because of gene lethality or redundancy. Recently, a link has been established between endomembrane trafficking and gravitropism. To understand this link, we screened a library of 10,000 diverse chemicals for compounds that affected the gravitropism of Arabidopsis seedlings positively or negatively. Sixty-nine of 219 compounds from the primary screen were retested, and 34 of these were confirmed to inhibit or enhance gravitropism. Four of the 34 compounds were found to cause aberrant endomembrane morphologies. The chemicals affected gravitropism and vacuole morphology in concert in a tissue-specific manner, underscoring the link between endomembranes and gravitropism. One of the chemicals (5403629) was structurally similar to the synthetic auxin 2,4-dichlorophenoxy acetate, whereas the other three chemicals were unique in their structures. An in vivo functional assay using the reporter β-glucuronidase under the auxin-inducible DR5 promoter confirmed that the unique compounds were not auxins. Interestingly, one of the unique chemicals (5850247) appeared to decrease the responsiveness to auxin in roots, whereas another (5271050) was similar to pyocyanin, a bacterial metabolite that has been suggested to target the endomembranes of yeast. These reagents will be valuable for dissecting endomembrane trafficking and gravitropism and for cognate target identification.
KW - Chemicals
KW - GFP
KW - Gravitropism
KW - Trafficking
KW - Vacuoles
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U2 - 10.1073/pnas.0500222102
DO - 10.1073/pnas.0500222102
M3 - Article
C2 - 15772170
AN - SCOPUS:16344363588
SN - 0027-8424
VL - 102
SP - 4902
EP - 4907
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 13
ER -