James E. Huettner, Ph.D.
Cell Biology and Physiology
Molecular Cell Biology Program
Computational and Molecular Biophysics Program
My laboratory studies ion channels gated by glutamate receptors. In the vertebrate CNS, glutamate receptors in the postsynaptic membrane underlie the transmission of information at excitatory synapses. Our goal is to provide a better understanding of synapses by determining the properties of glutamate receptors and of the channels that they control. We use electrophysiological recordings to study the activation and desensitization of the receptors following rapid application of glutamate. We also study compounds that block the glutamate binding site or physically occlude the ion pore. More recently, we have concentrated on a subtype of glutamate receptor that exhibits a unique form of desensitization. Comparison of the different receptor subtypes should lead to a clearer picture of how the binding of glutamate operates the channels.
A second major goal of my lab is to understand the control of neuronal differentiation. We study the properties of neurons derived from human and mouse Embryonic Stem (ES) cells. We have shown that mouse ES-derived neurons express voltage-gated Na, K, and Ca channels, as well as channels gated by glutamate, GABA and glycine. Within two to three weeks after induction, some of the cells form excitatory synapses, whereas others form inhibitory connections. Using antibodies GAP43 and MAP-2 we have demonstrated the segregation of these proteins into separate axonal and somatodendritic compartments. In both their physiological properties and their ability to establish a polarized phenotype the differentiated mouse ES cells strongly resemble neurons from the CNS. Studies of human ES cell differentiation are ongoing.
McCreedy DA, Brown CR, Butts JC, Xu H, Huettner JE, Sakiyama-Elbert SE. (2014) A new method for generating high purity motoneurons from mouse embryonic stem cells. Biotechnol Bioeng. May 19. Epub ahead of print.
Huettner JE. (2014) Glutamate receptor pores. J Physiol. May 9. Epub ahead of print.
Wilding TJ, Lopez MN, Huettner JE. (2014) Radial symmetry in a chimeric glutamate receptor pore. Nat Commun. 5:3349.
Chandrasekar I, Huettner JE, Turney SG, Bridgman PC. (2013) Myosin II regulates activity dependent compensatory endocytosis at central synapses. J Neurosci. 33:16131-45.
Lopez MN, Wilding TJ, Huettner JE. (2013) Q/R site interactions with the M3 helix in GluK2 kainate receptor channels revealed by thermodynamic mutant cycles. Journal of General Physiology 142:225-39.
Solomon IH, Khatri N, Biasini E, Massignan T, Huettner JE, (2011) Harris DA. An N-terminal polybasic domain and cell surface localization are required for mutant prion protein toxicity. Journal of Biological Chemistry 286:14724-36.
Wilding TJ, Chen K, Huettner JE. (2010) Fatty acid modulation and polyamine block of GluK2 kainate receptors analyzed by scanning mutagenesis. Journal of General Physiology 136:339-52.
Kim M, Habiba A, Doherty JM, Mills JC, Mercer RW, Huettner JE. (2009) Regulation of mouse embryonic stem cell neural differentiation by retinoic acid. Developmental Biology 328: 456-474.
Laezza F, Wilding TJ, Sequeira S, Craig AM, Huettner JE. (2008) The BTB/kelch protein, KRIP6, modulates the interaction of PICK1 with GluR6 kainate receptors. Neuropharmacology 55:1131-1139.
Wilding TJ, Fulling E, Zhou Y, Huettner JE. (2008) Amino acid substitutions in the pore helix of GluR6 control inhibition by membrane fatty acids. J General Physiology 132: 85-99.
Last Updated: 8/18/2014 11:04:43 AM
Cross section through the pore of GluK2(R) highlighting M3 residues that interact with the Q/R editing site