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Thomas Soderling is a senior scientist in the Vollum Institute. He holds concurrent appointments in the Department of Biochemistry and Molecular Biology and Cell and Developmental Biology in the School of Medicine. After receiving his B.S. in Chemistry from the University of Idaho in 1966, Soderling pursued his Ph.D. in Biochemistry at the University of Washington and graduated in 1970. He arrived at the Vollum in 1991 after 17 years at Vanderbilt Medical School as a professor of Molecular Physiology and Biophysics. From 1976 to 1989, he was an investigator in the Howard Hughes Medical Institute.
Research Interests
Intracellular calcium (Ca2+) is vital to many regulatory pathways inside cells. Mammalian cells contain a protein called calmodulin (CaM) which has a very high affinity for binding Ca2+. As the Ca2+ concentration inside the cell rises, Ca2+ and CaM form a complex, Ca2+/CaM. This complex interacts with, and alters, the functions of a large number of proteins inside cells. The Soderling lab focuses on cellular functions of protein kinases activated by binding Ca2+/CaM. By adding phosphate groups to other proteins, these Ca2+/CaM-stimulated protein kinases (CaMKs) modulate a variety of cellular functions including ion channels, transcription factors, structural proteins, and proteins (enzymes) that control the chemistry of the cell. The lab studies the regulatory properties of these CaMKs and their targets (substrates) in brain cells. Understanding the biology of these signaling pathways should clarify their physiological functions in cells. Studies in the lab rely on techniques of protein chemistry, molecular biology, fluorescent imaging, and electrophysiology.
Soderling and his colleagues are looking at the cellular effects of these Ca2+/CaM kinases. Recent studies indicate that CaMKI is required for proper development of nerve projections (axons and dendrites) by regulating the cytoskeleton in the growth cone. CaMKII, by phosphorylating glutamate receptor ion channels (AMPA receptors), regulates synaptic current in learning and memory paradigms such as long-term potentiation (LTP). Prolonged expression of LTP also requires initiation of gene transcription and protein synthesis. CaMKII appears to regulate dendritic protein synthesis through the mRNA translation factor CPEB, whereas another member of the CaMK family, CaMKIV, stimulates gene expression in the nucleus. Thus, these three Ca2+ responsive protein kinases participate in distinct steps of the complex process of learning and memory in the brain.
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Selected Publications
Derkach, V.A., Oh, M.C., Guire, E.S., and Soderling, T.R. (2007) Regulatory mechanisms of AMPA receptors in synaptic plasticity. Nature Rev. Neurosci. 8:101-113.
Wayman, G.A., Impey, S., Marks, D., Saneyoshi, T., Grant, W.F., Derkach, V., and Soderling, T.R. (2006) Activity-dependent dendritic arborization mediated by CaM-kinase I activation and enhanced CREB-dependent transcription of Wnt-2. Neuron 50:897-909. (see commentaries in Neuron 50:813-5; Science STKE 2006(342):tw220; and Nature Rev. Neurosci. 7:598.)
Schmitt, J.M., Guire, E.S., Saneyoshi, T., and Soderling, T.R. (2005) CaM Kinase Kinase/CaM Kinase I activity gates ERK-dependent long-term potentiation. J. Neurosci. 25:1281-1290.
Atkins, C.M., Davare, M.A., Oh, M.C., Derkach, V., and Soderling, T.R. (2005) Bidirectional regulation of CPEB phosphorylation by CaMKII and PP1 during hippocampal LTP. J. Neurosci. 25:5604-10.
Wayman, G.A, Kaech, S., Grant, W.F., Davare, M., Impey, S. Tokumitsu, H., Nozaki, N., Banker, G., and Soderling, T.R. (2004) Regulation of axonal extension and growth cone motility by calmodulin-dependent protein kinase I. J. Neurosci. 24:3786-3794.
Impey, S., Fong, A.L., Wang, Y., Cardinaux, J.R., Fass, D.M., Obrietan, K., Wayman, G.A., Storm, D.R., Soderling, T.R., and Goodman, R.H. (2002) Phosphorylation of CBP mediates transcriptional activation by neural activity and CaM-kinase IV. Neuron 34:235-244.
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