Edinburgh, Scotland, United Kingdom - TAIR
Edinburgh, Scotland, United Kingdom - TAIR
Edinburgh, Scotland, United Kingdom - TAIR
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Sidestepping genetic redundancy with small<br />
molecules<br />
Genetic redundancy is pervasive in plants and can limit the ability of forward<br />
genetic analysis to identify factors in a pathway. Small molecules can combat this<br />
genetic redundancy, because their variable selectivity can illuminate functions for<br />
otherwise redundant gene products. For example, an antagonist with low<br />
selectivity can perturb the function of an entire protein family, while a selective<br />
agonist can illuminate the function of one member of normally redundant<br />
receptors, as we describe with our work on the selective ABA agonist pyrabactin.<br />
Pyrbactin acts through PYRABACTIN RESISTANCE 1 (Pyr1), the founding<br />
member of a family of START proteins called PYR/PYLs, which are necessary<br />
for both pyrabactin and ABA signaling in vivo. Our data show that ABA binds to<br />
PYR1, which in turn binds to and inhibits PP2Cs. We conclude that PYR/PYLs<br />
are ABA receptors that function at the apex of a negative regulatory pathway<br />
that controls ABA signaling by inhibiting PP2Cs. When assayed for ABA<br />
sensitivity, Pyr/Pyl genes show redundancy, which we suggest prevented these<br />
genes from emerging in ABA screens conducted over the last 20 years.<br />
Pyrabactin’s selectivity for a subset of the PYR/PYL family enabled us to bypass<br />
this redundancy, which masks ABA phenotypes in single mutants. Thus, our<br />
results demonstrate the power of synthetic molecules to expose phenotypes for<br />
otherwise redundant genes.<br />
64<br />
C13<br />
Wednesday 16:30 - 17:00<br />
Tools and Resources<br />
Sean Cutler1<br />
Sang-Youl Park1<br />
Pauline Fung2<br />
Davin Jensen3<br />
Brian Volkman3<br />
Noriyuki Nishimura4<br />
Julian Schroeder4<br />
Pedro Rodriguez5<br />
Nicholas Provart2<br />
Jian-Kang Zhu1<br />
Hiroaki Fujii1<br />
Ruth Finkelstein6<br />
Shelley Lumba2<br />
Darrell Desveaux2<br />
Peter McCourt2<br />
Juila Santiago5<br />
Americo Rodrigues5<br />
Dario Bonetta7<br />
Simon Alfred2<br />
Yang Zhao2<br />
Tsz-Fung Chow2<br />
1University of California-<br />
Riverside<br />
2University of Toronto,<br />
3Medical College of<br />
Wisconsin<br />
4University of California -<br />
San Diego<br />
5Universidad Politecnica<br />
6University of California -<br />
Santa Barbara<br />
7University of Ontario<br />
Institute of Technology
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