The broad, long-term objective is to understand the mechanisms by which organisms control transition metal ions and the roles of these metals, particularly copper, in cell signaling and regulatory pathways. Copper homeostasis is of major importance to human health, yet the pathways for intracellular copper trafficking are unclear, and relatively few components in copper sensing and trafficking have been identified. This proposal focuses on RTE, a previously undescribed gene of novel sequence, which is hypothesized to encode a sensor, transporter or chaperone for copper. The RTE gene is highly conserved, and is present in a single copy in animals and in two copies in plants.
The aim of this proposal is to define the role of RTE in metal homeostasis. The studies will center primarily on the RTE1 gene of the model plant Arabidopsis thaliana. Genetic analyses in Arabidopsis have linked RTE1 to two copper-binding proteins in ethylene signal transduction. One is the copper-requiring ethylene receptor ETR1, whose function is dependent on RTE1. The other is RAN1, a homolog of the human Menkes/Wilson's P-type ATPase copper transporter, which is likewise required for ethylene receptor function. Investigating the genetic and cellular basis for these connections to RTE1 in Arabidopsis will utilize powerful genetic tools for understanding the cellular roles of RTE. Parallel experiments with respect to RTE and the Menkes/Wilson's homolog CUA-1 will be performed in the animal genetic model Caenorhabditis elegans, allowing comparison and integration of results from an animal system with those in plants. Saccharomyces cerevisiae and mammalian cell culture will be employed for ethylene binding assays and copper binding assays, respectively. The proposed experiments will use a combination of molecular genetics, cell biology and biochemical methods. The elucidation of RTE function should have a direct impact on understanding the processes of metal homeostasis for the benefit of human health.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM071855-03S1
Application #
7480534
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Anderson, James J
Project Start
2005-04-01
Project End
2009-03-31
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
3
Fiscal Year
2007
Total Cost
$32,125
Indirect Cost
Name
University of Maryland College Park
Department
Anatomy/Cell Biology
Type
Schools of Earth Sciences/Natur
DUNS #
790934285
City
College Park
State
MD
Country
United States
Zip Code
20742
Wang, Feifei; Wang, Lijuan; Qiao, Longfei et al. (2017) Arabidopsis CPR5 regulates ethylene signaling via molecular association with the ETR1 receptor. J Integr Plant Biol 59:810-824
Zheng, Fangfang; Cui, Xiankui; Rivarola, Maximo et al. (2017) Molecular association of Arabidopsis RTH with its homolog RTE1 in regulating ethylene signaling. J Exp Bot 68:2821-2832
Chang, Jianhong; Clay, John M; Chang, Caren (2014) Association of cytochrome b5 with ETR1 ethylene receptor signaling through RTE1 in Arabidopsis. Plant J 77:558-67
Cela, Jana; Chang, Caren; Munne-Bosch, Sergi (2011) Accumulation of ýý- rather than ýý-tocopherol alters ethylene signaling gene expression in the vte4 mutant of Arabidopsis thaliana. Plant Cell Physiol 52:1389-400
Dong, Chun-Hai; Jang, Mihue; Scharein, Benjamin et al. (2010) Molecular association of the Arabidopsis ETR1 ethylene receptor and a regulator of ethylene signaling, RTE1. J Biol Chem 285:40706-13
Rivarola, Maximo; McClellan, Christopher A; Resnick, Josephine S et al. (2009) ETR1-specific mutations distinguish ETR1 from other Arabidopsis ethylene receptors as revealed by genetic interaction with RTE1. Plant Physiol 150:547-51
Gao, Zhiyong; Wen, Chi-Kuang; Binder, Brad M et al. (2008) Heteromeric interactions among ethylene receptors mediate signaling in Arabidopsis. J Biol Chem 283:23801-10
Resnick, Josephine S; Rivarola, Maximo; Chang, Caren (2008) Involvement of RTE1 in conformational changes promoting ETR1 ethylene receptor signaling in Arabidopsis. Plant J 56:423-31
McClellan, Christopher A; Chang, Caren (2008) The role of protein turnover in ethylene biosynthesis and response. Plant Sci 175:24-31
Dong, Chun-Hai; Rivarola, Maximo; Resnick, Josephine S et al. (2008) Subcellular co-localization of Arabidopsis RTE1 and ETR1 supports a regulatory role for RTE1 in ETR1 ethylene signaling. Plant J 53:275-86

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