Eric C. Beattie, Ph.D.
Email: Beattie@cpmcri.org

Introduction  |  Publications 

Introduction

My work focuses on the functioning of the synapse, a structure that allows for communication between neurons. The class of neurotransmitter receptors which focus on function in the synapse. These are the glutamate receptors. The plasticity, or the adjustable strength, of the synapse is thought to be a key factor in the brain's ability to learn and store information. We are just beginning to understand the mechanisms which govern the functioning of this important juncture between neurons. My work has centered upon the trafficking of the AMPA-type glutamate receptors in hippocampal neurons. We have been able to show recently that AMPA receptors respond to different patterns of activity and neurotransmitter application to either come to the surface of the neuron or hide inside the cell. In this fashion, AMPA receptors can directly affect the strength of the synapse that they inhabit.

My current project brings together this previous interest in the role of glutamate receptors in memory formation with the protein TNF (tumor necrosis factor alpha). TNF is a protein that originally was discovered as an immune system modulator with functions outside the brain. We now have data that suggests that TNF is resident in brain tissue and has minute-to-minute control over the strength of communication between neurons (by controlling AMPAR trafficking). We believe that this protein is supplied to neurons in the brain in normal healthy situations by the surrounding and supportive astroglial cells, and that this activity may modulate such basic processes as memory formation. Finally, the possible implications for injury are substantial since previous studies show that after injury, TNF levels go way up in the brain. Together, those studies and our new data suggest a role for AMPA receptors in neuron excitotoxicity in situations where TNF concentrations are excessive, like after head trauma, stroke, or spinal cord injury.



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Publications 

Click here for a List of publications by Eric C Beattie in PubMed.

Representative Publications include:

Pingwei Zhao, Sheila Ignacio, Eric C. Beattie* and Mary E. Abood*
(*equal senior authors). Altered presymptomatic AMPA and cannabinoid receptor trafficking in motor neurons of ALS model mice: implications for excitotoxicity. European Journal of Neuroscience. 2008 Feb;27(3):572-9.

Dmitri Leonoudakis, Pingwei Zhao, and Eric C. Beattie. Rapid TNF-induced exocytosis of GluR2-lacking AMPARs to extrasynaptic plasma membrane potentiates excitotoxicity. The Journal of Neuroscience, 2008 Feb 27;28(9):2119-30.

Eric C. Beattie and David Stellwagen. AMPAR Synaptic and Surface Localization Is Altered by Glial-Derived Tumor Necrosis Factor Alpha: Relevance to Hyperalgesia and Central Sensitization. Part IV, Chapter 12. Invited authorship book chapter featured in Immune and Glial Regulation of Pain, edited by Linda Watkins, Joyce DeLeo, and Linda Sorkin. Seattle: International Association for the Study of Pain Press. ISBN-10 0-931092-67-1. This book is available for purchase at: http://www.iasp-pain.org/.

Guillermo A. Yudowski, Manojkumar A. Puthenveedu, Dmitri Leonoudakis, Sandip Panicker, Kurt S. Thorn, Eric C. Beattie and Mark von Zastrow. Real-time imaging of discrete exocytic events mediating surface delivery of AMPA receptors. J Neurosci. 2007 Oct 10;27(41):11112-21.

Zhu J, Beattie EC, Yang Y, Wang HJ, Seo JY, Yang XL. Centrosome impairments and consequent cytokinesis defects are possible mechanisms of taxane drugs. Anticancer Research. 2005 May-Jun;25(3B):1919-25.

Stellwagen D, Beattie EC, Seo JY, Malenka RC. Differential regulation of AMPA receptor and GABA receptor trafficking by tumor necrosis factor . Journal of Neuroscience, 2005 Mar 23;25(12):3219-28.

Leonoudakis D, Braithwaite SP, Beattie MS, Beattie EC. TNF-induced AMPAR trafficking in CNS neurons; relevance to excitotoxicity. Neuron Glia Biology, 2004 Aug;1(3):263-273.

Beattie EC, Stellwagen S, Morishita W, Bresnahan JC, Byeong-Kung Ha, Von Zastrow M, Beattie MS, Malenka RC. Control of Synaptic Strength by Glial TNF Science. Vol. 295, March 22, 2002.

Carroll RC, Beattie EC, von Zastrow M, Malenka RC. Role of AMPA Receptor Endocytosis In Synaptic Plasticity. Nature Neuroscience Reviews. May, 2001.

Beattie EC, Carroll RC, Yu X, Morishita W, Yasuda H, von Zastrow M, Malenka RC. Regulation of AMPA receptor endocytosis by a signaling mechanism shared with LTD. Nature Neuroscience 2000 Dec;3(12):1291-300.

Beattie EC, Howe CL, Wilde A, Brodsky FM, Mobley WC. NGF signals through TrkA to increase clathrin at the plasma membrane and enhance clathrin-mediated membrane trafficking. Journal of Neuroscience 2000 Oct 1;20(19):7325-33.

Whistler J, Beattie EC, and von Zastrow M. Tales from the Crypt: Evidence for Heptahelical Receptor Signaling in the Endocytic Pathway. Science Magazine's Signal Transduction Knowledge Environment: 2000 Aug 29,

Luscher C, Xia H, Beattie EC, Carroll RC, von Zastrow M, Malenka RC, Nicoll RA. Role of AMPA receptor cycling in synaptic transmission and plasticity. Neuron 1999 Nov;24(3):649-58.

Carroll RC, Beattie EC, Xia H, Luscher C, Altschuler Y, Nicoll RA, Malenka RC, von Zastrow M. Dynamin-dependent endocytosis of ionotropic glutamate receptors. Proc Natl Acad Sci U S A 1999 Nov 23;96(24):14112-

Wilde A, Beattie EC, Lem L, Riethof DA, Liu SH, Mobley WC, Soriano P, Brodsky FM. EGF receptor signaling stimulates SRC kinase phosphorylation of clathrin, influencing clathrin redistribution and EGF uptake. Cell 1999 Mar 5;96(5):677-87.

Grimes ML, Zhou J, Beattie EC, Yuen EC, Hall DE, Valletta JS, Topp KS, LaVail JH, Bunnett NW, Mobley WC. Endocytosis of activated TrkA: evidence that nerve growth factor inducesformation of signaling endosomes. J Neurosci 1996 Dec 15;16(24):7950-64

Grimes ML, Beattie E, WC Mobley. A signaling organelle containing the nerve growth factor-activated receptor tyrosine kinase, TrkA.
Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9909-14.

Beattie EC, Zhou J, Grimes ML, Bunnett NW, Howe CL, Mobley WC. A signaling endosome hypothesis to explain NGF actions: potential implications for neurodegeneration. Cold Spring Harb Symp Quant Biol 1996;61:389-406.
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