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Paul G. Mermelstein, Ph.D.
Associate Professor, Department of Neuroscience
pmerm@umn.edu
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Mermelstein Lab, July 2005(from L to R):
Jason Weick, Sidney Kuo, Rachel Groth, Katherine Bradley, Marissa Iden, Paul Mermelstein |
Calcium Signaling and Cellular Excitability.
Mammalian neurons face the daunting task of integrating signals from
tens of thousands of synaptic contacts. Based upon the temporal and
spatial cues by which neurotransmitters are released, as well as inputs
from more systemic signals (e.g. hormones) cells decide whether to
become quiescent, fire one or a series of action potentials and/or
alter their responses to future stimuli. But for long term changes
in synaptic plasticity to occur, new proteins must be generated.
My lab focuses on elucidating (1) the mechanisms by which neurons
decipher synaptic cues that are meant to activate protein synthesis
(2) the second messenger systems that relay signals from the synapse
to the nucleus leading to activity-dependent gene expression and (3)
the functional consequences of expressing these transcripts into protein.
Using a wide variety of powerful cellular and molecular techniques,
we have found that repeated stimulation of excitatory synapses causes
calcium to enter a cell through multiple ligand-voltage-gated ion
channels. However, only calcium entering through a specific class
of calcium channel (L-type) triggers the signal transduction pathways
that lead to the activation of several different transcription factors
and the synthesis of new protein.
Currently, we are focusing our attention on two separate transcription
factors, CREB and NF-AT, both of which have been implicated in memory
consolidation. Signaling to CREB and NF-AT rely heavily upon the calcium-binding
protein calmodulin. However, while CREB-dependent gene expression
is regulated by a series of calmodulin-dependent protein kinases,
NF-AT activation is through the calmodulin-dependent protein phosphatase
calcineurin. Future research will examine how L-type calcium channels
differentially regulate these transcription factors, the mechanism
by which L-type channels are 'privileged' in their ability to signal
changes in the nucleus, and the alterations in cellular excitability
that occur following CREB- and NF-AT-dependent gene expression. To
do so, the lab will employ electrophysiological, fluorescent imaging,
gene manipulation and transfection as well as DNA microarray techniques.Research
examining this form of neuroplasticity will undoubtedly help neuroscientists
better understand a variety of experimental themes such as learning
and memory, neuronal development and drug addiction. |
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Selected Publications
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Luoma J.I., Stern C.M. and Mermelstein P.G. (2011)
Progesterone inhibition of neuronal calcium signaling underlies aspects of progesterone-mediated neuroprotection.
J. Steroid Biochem. Mol. Biol. 2011 Nov 12. [Epub ahead of print] |
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Srivastava D.P., Waters E.M., Mermelstein P.G., Kramár E.A., Shors T.J. and Liu F. (2011)
Rapid estrogen signaling in the brain: implications for the fine-tuning of neuronal circuitry.
J Neurosci. 31(45):16056-63 |
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Stern C.M., Meitzen J. and Mermelstein P.G. (2011)
Corticotropin-releasing factor and urocortin I activate CREB through functionally selective Gβγ signaling in hippocampal pyramidal neurons.
Eur. J. Neurosci. 34(5):671-81 |
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Fauser B.C., et al. (2011)
Sex steroid hormones and reproductive disorders: impact on women's health.
Reprod. Sci. 18(8): 702-12. |
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Kelley B.G. and Mermelstein P.G. (2011)
Progesterone blocks multiple routes of ion flux.
Mol. Cell. Neurosci. 48(2):137-41 |
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Meitzen J. and Mermelstein P.G. (2011)
Estrogen receptors stimulate brain region specific metabotropic glutamate receptors to rapidly initiate signal transduction pathways.
J. Chem. Neuroanat. 42(4): 236-41 |
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Luoma J.I., Kelley B.G. and Mermelstein P.G. (2011)
Progesterone inhibition of voltage-gated calcium channels is a potential neuroprotective mechanism against excitotoxicity.
Steroids 76(9): 845-55 |
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Meitzen J., Luoma J.I., Stern C.M. and Mermelstein P.G. (2011)
ß1-Adrenergic receptors activate two distinct signaling pathways in striatal neurons.
J. Neurochem. 116(6):984-95 |
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Stern C.M. and Mermelstein P.G. (2010)
Caveolin regulation of neuronal intracellular signaling.
Cell. Mol. Life Sci. 67(22): 3785-95 |
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Groth R.D., Weick J.P., Bradley K.C., Luoma J.I., Aravamudan B., Klug J.R., Thomas M.J. and Mermelstein P.G. (2008)
D1 dopamine receptor activation of NFAT-mediated striatal gene expression.
Eur. J. Neurosci. 27(1): 31-42 |
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Mermelstein P.G. and Micevych P.E. (2008)
Nervous system physiology regulated by membrane estrogen receptors.
Rev. Neurosci. 19(6): 413-24 |
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Boulware M.I., Kordasiewicz H. and Mermelstein P.G. (2007)
Caveolin proteins are essential for distinct effects of membrane estrogen receptors in neurons.
J. Neurosci. 27(37): 9941-50 |
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Dewing P., Boulware M.I., Sinchak K., Christensen A., Mermelstein P.G. and Micevych P. (2007)
Membrane estrogen receptor-alpha interactions with metabotropic glutamate receptor 1a modulate female sexual receptivity in rats.
J. Neurosci. 27(35): 9294-300 |
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Groth R.D., Coicou L.G., Mermelstein P.G. and Seybold V.S. (2007)
Neurotrophin activation of NFAT-dependent transcription contributes to the regulation of pro-nociceptive genes.
J. Neurochem. 102(4): 1162-74 |
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Seybold V.S., Coicou L.G., Groth R.D. and Mermestein P.G. (2006)
Substance P initiates NFAT-dependent gene expression in spinal neurons.
J. Neurochem. 97: 397-407 |
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Boulware, M.I. and Mermestein P.G. (2005)
The influence of estradiol on nervous system function.
Drug News Perspect. 10: 631-37 |
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Bradley K.C., Groth R.D. and Mermelstein P.G. (2005)
Immunolocalization of NFATc4 in the adult mouse brain.
J. Neurosci. Res. 83: 762-70
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Boulware M.I., Weick J.P., Becklund B.R., Kuo S.P., Groth R.D. and Mermelstein P.G. (2005)
Estradiol activates group I and II metabotropic glutamate receptor signaling, leading to opposing influences on cAMP response element-binding protein.
J. Neurosci. 25: 5066-78 |
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Bradley K.C., Boulware M.B., Jiang H., Doerge R., Meisel R.L. and Mermelstein P.G. (2005)
Changes in gene expression within the nucleus accumbens and striatum following sexual experience.
Genes Brain Behav. 4(1): 31-44 |
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Groth R.D., Dunbar R.L. and Mermelstein, P.G. (2003)
Calcineurin regulation of neuronal plasticity.
Biochem. Biophys. Res. Commun. 311(4): 1159-71 |
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Groth R.D. and Mermelstein PG. (2003)
Brain-derived neurotrophic factor activation of NFAT (nuclear factor of activated T-cells)-dependent transcription: a role for the transcription factor NFATc4 in neurotrophin-mediated gene expression.
J. Neurosci. 23(22): 8125-34 |
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Weick J.P., Groth R.D., Isaksen A.L. and Mermelstein P.G. (2003)
Interactions with PDZ proteins are required for L-type calcium channels to activate cAMP response element-binding protein-dependent gene expression.
J. Neurosci. 23(8): 3446-56 |
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