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John Adelman received his Ph.D. in Microbiology from OHSU in 1988. He holds a B.S. and an M.S. in Microbiology from the University of Connecticut. After a year as a research assistant at Yale University, he spent five years as a research associate at Genentech. He arrived at the Vollum Institute in 1985, where he did his graduate research. After receiving his Ph.D., he accepted a faculty position at the Vollum and was promoted to senior scientist in 1998. Adelman holds concurrent appointments in the Departments of Cell and Developmental Biology and Molecular and Medical Genetics in the School of Medicine. Research InterestsSmall-conductance calcium-activated potassium channels (SK channels) are gated solely by intracellular Ca2+ ions and are fundamental regulators of neuronal excitability. Adelman and colleagues cloned the SK channel family and currently focus on four projects. The first project addresses the structure and function of SK channel calcium gating. Results have shown that calcium gating is mediated by calmodulin (CaM), which functions as an intrinsic subunit of the channel. The crystal structure of the SK CaMBD (CaM binding domain)-Ca2+/CaM complex suggested that four independent CaMBD-CaM subunits form a dimer-of-dimers upon Ca2+ binding to CaM, and this rearrangement opens the channel gate. This model is being rigorously tested using a repertoire of biochemical and electrophysiological techniques. Second, the lab is testing the hypothesis that a given subtype of SK channel can serve multiple roles in the same neuron by differential subcellular localization and interactions with distinct sets of microdomain partner proteins, forming an array of Ca2+ signaling complexes. This is being approached by a combination of proteomics, cell biology, and electrophysiology, using wild type and transgenic mice. In this project, a second beta subunit has been discovered, protein kinase CK2, that tightly binds to the SK channel-CaM complex. In this complex, CK2 phosphorylates CaM to alter channel activity. A novel mechanism for integrating metabolic signals may operate through CK2, and this is being investigated using biochemical, electrophysiological, and crystallographic approaches. Third, transgenic mice for each of the SK genes have been constructed using homologous recombination, allowing each of the SK genes to be manipulated experimentally. These animals have already delineated several important physiological functions of the channels including influences on synaptic plasticity, and learning and memory. Present experiments are investigating the mechanisms by which one of the subtypes, SK2 channels, alters the induction of synaptic plasticity and hippocampal-dependent memory encoding. A final focus, in collaboration with James Maylie, involves the study of mutant potassium channels responsible for the disease episodic ataxia (EA). Initial studies documented the functional differences between EA and wild type channels. Present efforts are directed toward understanding how the mutant potassium channels in cerebellar neurons lead to ataxia. To this end, Adelman and coworkers have constructed transgenic EA mice. These mice will be used to understand the basis for the therapeutic effects of carbonic anhydrase inhibitors. Selected PublicationsBond, C.T., Herson, P.S., Strassmaier, T., Hammond, R., Stackman, R., Maylie, J., and Adelman, J.P. (2004) SK2 Channels Underlie the Apamin-sensitive Current in Hippocampal CA1 Pyramidal Neurons. J. Neurosci. 24:5301-5306. Bildl, W., Strassmaier, T., Schulte, U., Andersen, J., Derst, C., Eble, S., Mann, M., Adelman, J.P., and Fakler, B. (2004) Protein kinase CK2 co-assembles with SK2 and regulates Ca2+-dependent gating. Neuron 43:847-858. Lee, W.-S., Ngo-Anh, T.J., Bruening-Wright, A., Maylie, J., and Adelman, J.P. (2003) Small conductance Ca2+-activated K+ channels and calmodulin: Cell surface expression and gating. J. Biol. Chem. 278:25940-25946. Schumacher, M.A., Rivard, A.F., and Adelman, J.P. (2001) Structure of the gating domain from small-conductance Ca2+-activated K+ channels complexed with Ca2+-calmodulin. Nature 410:1120-1124. Bond, C.T., Sprengel, R., Bissonnette, J.M., Kaufmann, W.A., Pribnow, D., Neelands, T., Storck, T., Baetscher, M., Jerecic, J., Maylie, J., Knauss, H.-G., Seeburg, P.H., and Adelman, J.P. (2000) Respiration and parturition affected by conditional overexpression of the small conductance Ca2+-activated K+ channel subunit, SK3. Science 289:1942-1946. Xia, X.-M., Fakler, B., Wayman, G., Johnson-Pais, T., Keen, J.E., Ishii, T., Hirschberg, B., Bond, C.T., Lutsenko, S., Maylie, J.P., and Adelman, J.P. (1998) Mechanism of calcium-gating in small conductance calcium-activated potassium channels. Nature 395:503-507. Köhler, M., Hirschberg, B., Bond, C.T., Kinzie, J.M., Marrion, N., Maylie, J., and Adelman, J.P. (1996) Small conductance, calcium-activated potassium channels from mammalian brain. Science 273:1709-1714.
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