Michael Byrne Robinson, Ph.D.

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Professor of Pediatrics
Department: Pediatrics
Graduate Group Affiliations

Contact information
Abramson Research Center, Rm 502D
Division of Developmental and Behavioral Pediatrics
34th and Civic Center Boulevard
Philadelphia, PA 19104-4318
Office: (215) 590-2205
Fax: (215) 590-3779
Lab: (215) 590-3839
B.S. (Chemistry)
Bates College , 1980.
Ph.D. (Biochemistry)
University of Minnesota, 1985.
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Description of Research Expertise

Signaling pathways that regulate glutamate transporters and the relationship of these transporters to acute brain injury

Biochemical, cell biological, and molecular biological techniques. These include cell culture and transfection of cDNAs, construction of chimeric and mutant transporters, assays for activation of signaling pathways, measurement of transport activity, quantitation of cell surface expression of transporters, western blotting, confocal microscopy, high performance liquid chromatography, and assessment of cell death.

Glutamate and aspartate are the predominant excitatory neurotransmitters in the mammalian CNS. These two excitatory amino acids (EAAs) mediate most of the rapid depolarization that occurs in the CNS. In fact, the levels of these transmitters are 1000- to 10,000-fold higher than those of many other important neurotransmitters, including dopamine, serotonin, and acetylcholine. Paradoxically, these EAAs are also potent neurotoxins, both in vivo and in vitro. In fact, excessive activation of EAA receptors contributes to the neuronal degeneration observed after acute insults to the CNS, such as stroke and head trauma. We are interested in the normal physiology of EAAs and the role of these transmitters in neurodegeneration. Our laboratory has focused on understanding the regulation of extracellular levels of EAAs because it is this pool of EAAs that is toxic to neurons. Extracellular concentrations of glutamate and aspartate are normally maintained in the low micromolar range by a family of sodium-dependent high affinity transporters that are present on both neurons and glial cells. Our laboratory has developed evidence that neurons induce and maintain expression of one of the astrocytic transporters critical for limiting excitotoxicity. We have begun to define the mechanisms that contribute to this regulation. Our laboratory has also found that the function of several of the transporter subtypes can be rapidly (within minutes) altered by activation of certain kinases. This regulation is associated with a redistribution of these transporters to/or from the plasma membrane (see the image below). The long term goal of the laboratory is to develop new strategies for limiting glutamate-mediated damage by understanding the endogenous mechanisms that clear this excitotoxin.

Selected Publications

González M.I., and Robinson M.B.: Neurotransmitter transporters: Why dance with so many partners? Curr. Opin. in Pharm. 4: 30-35, 2004.

Kalandadze A, Wu Y., Fournier K., and Robinson M.B.: Identification of motifs involved in endoplasmic reticulum retention/forward trafficking of the GLT-1 subtype of glutamate transporter. J. Neurosci. 24: 5183-92, 2004.

González M.I., and Robinson M.B.: Phorbol myristate acetate-dependent interaction of protein kinase Cá and the neuronal glutamate transporter EAAC1. J. Neurosci 23: 5589-5593, 2003.

Susarla B.T.S., and Robinson M.B.: Rottlerin, an inhibitor of protein kinase Cä, inhibits astrocytic glutamate transport activity and reduces GLAST immunoreactivity by a mechanism that appears to be PKCä independent. J. Neurochem. 86: 635-645, 2003.

Crino P.B., Jin H., Robinson M.B., Coulter D., Brooks-Kayal A.: Increased expression of the neuronal glutamate transporter (EAAT3/EAAC1) in hippocampal and neocortical epilepsy. Epilepsia 43: 211-218, 2002.

Raper S.E. Yudkoff M., Chirmule N., Gao G.P., Nunes F., Hashal Z.J., Furth E.E., Propert K.J., Robinson M.B., Maosin S., Simoes H., Speocher L., Highes J., Tazelaar J., Wivel N.A., Wilson J.M., and Batshaw M.L.: A pilot study of in vivo liver-directed gene transfer with an adenoviral vector in partial ornithine transcarbamylase deficiency. Human Gene Therapy 13: 163-175, 2002.

Holt, D.E., Washabau R.J., Djali S., Dayrell-Hart B., Drobatz K., Heyes M.P., and Robinson M.B.: Cerebrospinal fluid glutamine, tryptophan, and tryptophan metabolite concentrations are altered in dogs with portosystemic shunts. JAMVA 63: 1167-1171, 2002.

González M.I., Kazanietz M.G., and Robinson M.B.: Regulation of the neuronal glutamate transporter, excitatory amino acid carrier-1 (EAAC1), by different protein kinase C subtypes. Mol. Pharm. 62: 901-910, 2002.

Kalandadze A., Wu Y., and Robinson M.B.: Protein kinase C activation decreases cell surface expression of the GLT-1 subtype of glutamate transporter: Requirement of a carboxy-terminal domain and partial dependence on serine-486. J. Biol. Chem. 277: 45741-45750, 2002.

Robinson M.B.: Regulated trafficking of neurotransmitter transporters: Common notes but different melodies. J. Neurochem. 80: 1-11, 2002.

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Last updated: 03/18/2014
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