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| Robert J. Wenthold, Ph.D., Senior Investigator |
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Dr. Wenthold received a B.S. degree from Loras College and his Ph.D. from Indiana University where he worked with Henry Mahler on the biochemistry of synaptic proteins. After postdoctoral work at the NIH with Jorgen Fex, he became a faculty member in the Department of Neurophysiology at the University of Wisconsin. He joined NINCDS as a Senior Investigator in 1984 and moved to NIDCD when the institute was created in 1989. He became Chief of the Laboratory of Neurochemistry in 1996 and Scientific Director of NIDCD in 1998. Dr. Wenthold's laboratory studies the assembly, trafficking and synaptic expression of glutamate receptors.
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Staff:
- Rana Al-Hallaq, Research Fellow, (301) 496-8494 alhallaq@mail.nih.gov
- Kai Chang, Senior Research Assistant, (301) 594-7096 changkai@nidcd.nih.gov
- Lisa Dunbar, Research Fellow, (301) 435-6598 dunbarl@mail.nih.gov
- Martin Horak, Visiting Fellow mh579h@nih.gov
- Ronald S. Petralia, Staff Scientist, (301) 496-3804 petralia@nidcd.nih.gov
- Gail Seabold, Postdoctoral Fellow, (301) 594-8303 seaboldg@mail.nih.gov
- Catherine Croft Swanwick, IRTA Fellow cs612q@nih.gov
- Philip Wang, Student, (301) 496-6530 wangph@mail.nih.gov
- Ya-Xian Wang, Senior Research Assistant, (301) 496-3805 wangyx@nidcd.nih.gov
- Zhaohong Yi, Research Fellow, (301) 594-8303 yizh@mail.nih.gov
- Chan-Ying Zheng, Visiting Fellow zhengchan@nidcd.nih.gov
Research Interests:
The Section on Neurotransmitter Receptor Biology studies the molecular mechanisms underlying the regulation of glutamate receptors at the synapse. This complex family of proteins mediates most excitatory neurotransmission in the central nervous system and has been shown to play a direct role in some forms of synaptic plasticity that may be associated with learning and memory. Our current research is focused on three areas: 1) Assembly of receptor complexes. Ionotropic glutamate receptors are formed by the assembly of several subunits into a complex of 4 or 5 subunits. Multiple complexes of different subunit configurations are found within the same neuron, and these complexes can be targeted to different populations of synapses. We are interested in determining how these different complexes are produced and the factors that may alter their production. 2) Delivery of receptors to the synapse. We are interested in how receptors are selectively trafficked through the various cellular compartments to their appropriate synaptic location. This includes the identification of proteins that interact with the receptors during this delivery and the modifications to the receptor that may alter this delivery. 3) Stabilization of receptors at the synapse. Receptors are concentrated at the postsynaptic membrane probably through an interaction with proteins of the postsynaptic density. We are interested in the identity of these proteins and how these interactions are regulated. Removal of receptors from the synapse through internalization is likely to involve a disruption of the association with the anchoring protein. Our research involves primarily molecular techniques but relies heavily on morphological and physiological approaches. Immunogold electron microscopy, confocal microscopy, and cell culture complement our standard biochemical and cell biological experiments.
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Selected Recent Publications:
Wang, C.-Y., Chang, K., Petralia, R.S., Wang, Y.-X., Seabold, G.K. and Wenthold, R.J. (2006) A novel family of adhesion-like molecules that interacts with the NMDA receptor. , Journal of Neuroscience 26, 2174-2183.
Prybylowski, K., Chang, K., Sans, N., Kan, L., Vicini, S., and Wenthold R.J. (2005) The synaptic localization of NR2B-containing NMDA receptors is controlled by interactions with PDZ proteins and AP-2., Neuron 47, 845-857.
Sans, N., Wang, P.Y., Du, Q., Petralia, R.S., Wang, Y.X., Nakka, S., Blumer, J.B., Macara, I.G. and Wenthold, R.J. (2005) mPins, the mammalian homologue of Drosophila Pins, modulates PSD-95 and SAP102 trafficking and influences NMDA receptor surface expression., Nature Cell Biology 7, 1179-1190.
Petralia, R.S., Sans, N., Wang, Y.X., and Wenthold, R.J. (2005) Ontogeny of postsynaptic density proteins at glutamatergic synapses., Mol. Cell Neuroscience 29, 436-452.
Hawkins, L.M., Prybylowski, K., Chang, K., Moussan, C., Stephenson, F.A., and Wenthold, R.J. (2004) Export from the endoplasmic reticulum of assembled NMDA receptors is controlled by a motif in the C-terminus of the NR2 subunit, Journal of Biological Chemistry 279, 28903-28910 .
Wenthold, R.J., Prybylowski, K., Standley, S., Sans, N., and Petralia, R.S (2003) Trafficking of NMDA receptors. , Annual Reviews of Pharmacology and Toxicology 43, 335-358 .
Sans, N., Prybylowski ,K., Petralia, R.S., Chang, K. Wang, Y.-X., Racca, C., Vicini, S., and Wenthold, R.J (2003) NMDA receptor trafficking through an interaction between PDZ Proteins and the exocyst complex. , Nature Cell Biology 5, 520-530 .
All Selected Publications
Contact Information:
Dr. Robert J. Wenthold
Neurotransmitter Receptor Biology Section
Laboratory of Neurochemistry, NIDCD
Building 50, Room 4140
50 South Drive MSC 0000
Bethesda, MA 20892-4162
Telephone: (301) 496-6530 (office),
(301) 480-2324 (fax)
Email: wenthold@nidcd.nih.gov
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