of Work: In the Membrane Signaling Group, we study the signal transduction pathways which regulate cell function without altering gene expression. Ion channel proteins are the effectors for many of these pathways, regulating electrical signaling in the brain, hormone secretion, cardiovascular contractility, epithelial transport, and cell migration. Inherited mutations in channel encoding genes are responsible for many serious human diseases. We focus on the signaling pathways linking G protein coupled receptors to ion channel regulation through calcium and reversible protein phosphorylation. The patch clamp technique allows us to measure the activity of individual channel proteins in real time in situ in live cells. We have discovered that G proteins stimulate potassium channels through protein phosphatases, which are the targets of many aquatic microbial toxins. In particular we have identified the molecular basis for regulation of calcium- and voltage-activated potassium channels by reversible protein phosphorylation. In addition we have identified a new G protein dependent signaling mechanism for thyroid hormone, which could explain its importance for neural development.
| 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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