of Work: In the Membrane Signaling Group, we investigate the biochemical mechanisms that allow the human body to maintain physiological homeostasis, or, in modern terms, the molecular basis of cell communication. In particular we study the signaling pathways that regulate cell function without altering gene expression. Ion channel proteins are the effectors for many of these pathways. We focus on the voltage-dependent channels that are selectively permeable to calcium or to potassium, and we use the patch clamp technique to study channel protein function and regulation at the molecular level in live cells in real time. We are most interested in G protein signaling cascades that regulate ion channel activity through calcium and reversible protein phosphorylation. G proteins are the trans-ducing proteins for the majority of chemical messengers used in cell communication, and receptor proteins that act through G proteins are the most common target of pharmaceuticals used clinically to treat human disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES080043-18
Application #
7169994
Study Section
(LST)
Project Start
Project End
Budget Start
Budget End
Support Year
18
Fiscal Year
2005
Total Cost
Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Lucas, Sarah J; Armstrong, David L (2015) Protein phosphatase modulation of somatostatin receptor signaling in the mouse hippocampus. Neuropharmacology 99:232-41
Chatterjee, Anindya; Wang, Ling; Armstrong, David L et al. (2010) Activated Rac1 GTPase translocates protein phosphatase 5 to the cell membrane and stimulates phosphatase activity in vitro. J Biol Chem 285:3872-82
Armstrong, David L; Erxleben, Christian; White, Jody A (2010) Patch clamp methods for studying calcium channels. Methods Cell Biol 99:183-97
Sanchez-Ortiz, Efrain; Hahm, Byoung Kwon; Armstrong, David L et al. (2009) Protein phosphatase 5 protects neurons against amyloid-beta toxicity. J Neurochem 111:391-402
Liao, Yanhong; Erxleben, Christian; Yildirim, Eda et al. (2007) Orai proteins interact with TRPC channels and confer responsiveness to store depletion. Proc Natl Acad Sci U S A 104:4682-7
Erxleben, Christian; Liao, Yanhong; Gentile, Saverio et al. (2006) Cyclosporin and Timothy syndrome increase mode 2 gating of CaV1.2 calcium channels through aberrant phosphorylation of S6 helices. Proc Natl Acad Sci U S A 103:3932-7
Gentile, Saverio; Darden, Thomas; Erxleben, Christian et al. (2006) Rac GTPase signaling through the PP5 protein phosphatase. Proc Natl Acad Sci U S A 103:5202-6
Storey, Nina M; Gomez-Angelats, Mireia; Bortner, Carl D et al. (2003) Stimulation of Kv1.3 potassium channels by death receptors during apoptosis in Jurkat T lymphocytes. J Biol Chem 278:33319-26
Erxleben, Christian; Gomez-Alegria, Claudio; Darden, Thomas et al. (2003) Modulation of cardiac Ca(V)1.2 channels by dihydropyridine and phosphatase inhibitor requires Ser-1142 in the domain III pore loop. Proc Natl Acad Sci U S A 100:2929-34
Tian, Lijun; Coghill, Lorraine S; MacDonald, Stephen H-F et al. (2003) Leucine zipper domain targets cAMP-dependent protein kinase to mammalian BK channels. J Biol Chem 278:8669-77

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