As neuroscience enters the post-genomic era, a major goal is the translation of genomic sequence information into a molecular understanding of the mechanisms of neuronal information processing and transfer. My laboratory’s research focuses on protein function, biochemical pathways and networks of protein-protein interactions regulating intra- and inter-cellular signaling in mammalian neurons. In particular, we are interested in dynamic regulation of voltage-sensitive ion channel abundance, localization and function through reversible protein phosphorylation. These proteins determine the intrinsic electrical properties of neurons and how these cells respond to external stimuli, integrate the encoded information and generate an appropriate response. Modern proteomic techniques have allowed for insights into protein networks, and post-translational modifications, that provide for both the generation and maintenance of complex cellular functions, but also their dynamic regulation that underlies functional plasticity. Our studies are aimed at a molecular understanding of how neuronal ion channels generate and maintain the fidelity of neuronal signaling, and how these processes can be dynamically regulated to generate neuronal plasticity. Such information is necessary for an increased understanding of not only the normal functional plasticity of neurons, but also in understanding of disease states where neuronal function is altered and effects of acute external insults such as ischemia and drugs of abuse, and represent a key step towards the development of therapeutics that can address these and other psychiatric and neurological disorders. Moreover, these studies are representative of approaches that would prove advantageous to studies on other neuronal signaling proteins. To better translate findings from genome-based studies, we have also established the UC Davis/NIH NeuroMab facility, to use information on proteins encoded in the human and other genomes to generate monoclonal antibodies for use in the research community.
Mohapatra, D. P., and J. S. Trimmer. (2006). The Kv2.1 C-Terminus Can Autonomously Transfer Kv2.1-Like Phosphorylation-Dependent Localization, Voltage-Dependent Gating and Muscarinic Modulation to Diverse Kv Channels. J. Neurosci. 26:685-695.
Park, K.-S., Mohapatra, D. P., Misonou, H., and J. S. Trimmer. (2006). Graded Regulation of the Kv2.1 Potassium Channel by Variable Phosphorylation. Science 313:976-979.
Menegola, M., and J. S. Trimmer. (2006). Unanticipated Region- and Cell-specific Downregulation of Individual KChIP Auxiliary Subunit Isotypes in Kv4.2 Knockout Mouse Brain. J. Neurosci. 26:12137-12142.
Rhodes, K. J., and J. S. Trimmer. (2006). Antibodies as Valuable Neuroscience Research Tools versus Reagents of Mass Distraction. J. Neurosci. 26:8017-8020.
Misonou, H., Menegola, M., Mohapatra, D. P., Guy, L. K., Park, K.-S., and J. S. Trimmer. (2006). Bidirectional Activity-Dependent Regulation of Neuronal Ion Channel Phosphorylation. J. Neurosci. 26:13505-13514.
Vacher, H., Mohapatra, D. P., Misonou, H, and J. S. Trimmer. (2007). Regulation of Kv1 Channel Trafficking by the Mamba Snake Neurotoxin Dendrotoxin K. FASEB J. 21:906-914.
Yang, J.-W., *Vacher, H., Park, K.-S., Clark, E, and J. S. Trimmer. (2007). Trafficking-dependent Phosphorylation of Kv1.2 Regulates Voltage-gated Potassium Channel Cell Surface Expression. Proc. Nat. Acad. Sci. USA 104: 20055-20060.
Mohapatra, D. P., Siino, D. F., and J. S. Trimmer. (2008). Interdomain Cytoplasmic Interactions Govern the Intracellular Trafficking, Gating and Modulation of the Kv2.1 Channel. J. Neurosci. 28: 4982-4994.
Park, K.-S., Yang, J.-W., Seikel, E., and J. S. Trimmer. (2008). Potassium Channel Phosphorylation in Excitable Cells: Providing Dynamic Functional Variability to a Diverse Family of Ion Channels. Physiology 23:49-57.
Menegola, M., Misonou, H., Vacher, H., and J. S. Trimmer. (2008). Dendritic A-type Potassium Channel Subunit Expression in CA1 Hippocampal Interneurons. Neurosci. 154: 953-964.
Monaghan, M. M., Menegola, M., Vacher, H., Rhodes, K. J., and J. S. Trimmer. (2008). Altered Expression and Localization of Hippocampal A-Type Potassium Channel Subunits in the Pilocarpine-Induced Model of Temporal Lobe Epilepsy. Neurosci. 156: 550-562.
Rhodes, K. J., and J. S. Trimmer. (2008). Antibody-based Validation of CNS Ion Channel Drug Targets. J. Gen. Physiol. 131:407-413.
Yan, J., Olsen, J. V., Park, K.-S., Li, W., Bildl, W., Schulte, U., Aldrich, R. W., Fakler, B., and J. S. Trimmer. (2008). Profiling the Phospho-status of the BKCa Channel a Subunit in Rat Brain Reveals Unexpected Patterns and Complexity. Mol. Cell. Proteomics 7: 2188-2198.
Vacher, H., Mohapatra, D. P., and J. S. Trimmer. (2008). Localization and Targeting of Voltage-Gated Ion Channels in Mammalian Central Neurons. Physiol. Rev. 88: 1407-1447.
Mohapatra, D. P., Misonou, H, Pan, S.-J., Held, J. E., Surmeier, D. J., and J. S. Trimmer. (2009). Modulation of the Kv2.1 Potassium Channel Contributes to Activity-Dependent Regulation of Intrinsic Excitability in Hippocampal Neurons. Channels 3: 46-56.
Rasband, M. N., and J. S. Trimmer. (2009). Ion Channel Localization in Axons. (pp. 229-235). In Encyclopedia of Neuroscience, Volume 5. (L. R. Squire, Editor). Oxford: Academic Press, London.
Vacher, H., and J. S. Trimmer. (2009). Shaker Family Kv1 Voltage-gated Potassium Channels in Mammalian Brain Neurons. (Chapter 5, pp. 127-154). In Structure, Function and Modulation of Neuronal Voltage Gated Ion Channels. (V. Gribkoff and L. K. Kaczmarek, Editors). John Wiley and Sons, Hoboken.
Mikula, S., Parrish, S. K., Trimmer, J. S., and E. G. Jones. (2009). Complete 3D Visualization of Primate Striosomes by KChIP1 Immunostaining. J. Comp. Neurol. 514: 507-517.
Seikel, E. and J. S. Trimmer. (2009). Convergent Modulation of Kv4.2 Channel a Subunits by Structurally Distinct DPPX and KChIP Auxiliary Subunits. Biochemistry 48: 5721-5730.
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