The long-term goal of the proposed research is to understand how calcium, a universal messenger, regulates gene expression and cell activities. Calcium ions are pivotal in the regulation of a variety of cellular processes. Abnormal calcium homeostasis has been implicated in aging and in numerous human diseases, such as Alzheimer's disease. The enduring regulatory effects of calcium depend on changes in gene expression. The mechanisms by which cells decode the information carried by calcium signals and convert them into distinct alterations in gene expression is poorly understood. A prevailing model is that Ca2+ entry through different ion channels activates distinct transcription factors. Through the mediation of a series of protein kinases or phosphatases, Ca2+/calmodulin stimulates a range of transcription factors. Recent bioinformatic analyses have suggested the existence of transcription factors that are activated directly by Ca2+/calmodulin, which could respond to Ca2+ signals more quickly. A group of candidates, the calmodulin-binding transcription activators (CAMTAs) were recently identified in plants. Their homologs in animals have yet to be studied. We have isolated two Drosophila mutant alleles of dCAMTA, the fly CAMTA gene, and detected a strong and consistent phenotype in these mutants that implies an impaired deactivation of the fly light-stimulated Ca2+ channel TRP. Therefore we plan to use the fly photoreceptor cells as an assay system to study this new group of Ca2+-regulated transcription factors. A combination of molecular and cell biological, genetic, electrophysiological and calcium imaging approaches will be used to: 1. Test the hypothesis that dCAMTA is activated through Ca2+/calmodulin-binding in vivo. 2: Test the hypothesis that dCAMTA exists in the cytoplasm and translocates into the nuclei upon activation. 3: Test the hypothesis that dCAMTA proteins form homomultimers. 4. Test the hypothesis that dCAMTA depends on TRP channels for activation in the photoreceptor cells. 5. Test the hypothesis that the loss of dCAMTA function leads to increased Ca2+ level in the photoreceptor cells. 6. Determine the target genes of dCAMTA.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG022508-05
Application #
7268696
Study Section
Special Emphasis Panel (ZRG1-MDCN-4 (01))
Program Officer
Velazquez, Jose M
Project Start
2003-08-01
Project End
2009-07-31
Budget Start
2007-08-01
Budget End
2009-07-31
Support Year
5
Fiscal Year
2007
Total Cost
$339,212
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Biology
Type
Schools of Medicine
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655
Luan, Zhuo; Quigley, Caitlin; Li, Hong-Sheng (2015) The putative Na?/Cl?-dependent neurotransmitter/osmolyte transporter inebriated in the Drosophila hindgut is essential for the maintenance of systemic water homeostasis. Sci Rep 5:7993
Luan, Zhuo; Reddig, Keith; Li, Hong-Sheng (2014) Loss of Na(+)/K(+)-ATPase in Drosophila photoreceptors leads to blindness and age-dependent neurodegeneration. Exp Neurol 261:791-801
Chaturvedi, Ratna; Reddig, Keith; Li, Hong-Sheng (2014) Long-distance mechanism of neurotransmitter recycling mediated by glial network facilitates visual function in Drosophila. Proc Natl Acad Sci U S A 111:2812-7
Luan, Zhuo; Li, Hong-Sheng (2012) Inwardly rectifying potassium channels in Drosophila. Sheng Li Xue Bao 64:515-9
Hu, Wen; Wan, Didi; Yu, Xiaoming et al. (2012) Protein Gq modulates termination of phototransduction and prevents retinal degeneration. J Biol Chem 287:13911-8
Cao, Jinguo; Li, Yi; Xia, Wenjing et al. (2011) A Drosophila metallophosphoesterase mediates deglycosylation of rhodopsin. EMBO J 30:3701-13
Venkatachalam, Kartik; Wasserman, David; Wang, Xiaoyue et al. (2010) Dependence on a retinophilin/myosin complex for stability of PKC and INAD and termination of phototransduction. J Neurosci 30:11337-45
Ni, Lina; Guo, Peiyi; Reddig, Keith et al. (2008) Mutation of a TADR protein leads to rhodopsin and Gq-dependent retinal degeneration in Drosophila. J Neurosci 28:13478-87
Han, Junhai; Reddig, Keith; Li, Hong-Sheng (2007) Prolonged G(q) activity triggers fly rhodopsin endocytosis and degradation, and reduces photoreceptor sensitivity. EMBO J 26:4966-73
Gong, Ping; Han, Junhai; Reddig, Keith et al. (2007) A potential dimerization region of dCAMTA is critical for termination of fly visual response. J Biol Chem 282:21253-8

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