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Research ArticleArticle

Regulation of the Neuronal Glutamate Transporter Excitatory Amino Acid Carrier-1 (EAAC1) by Different Protein Kinase C Subtypes

Marco I. González, Marcelo G. Kazanietz and Michael B. Robinson
Molecular Pharmacology October 2002, 62 (4) 901-910; DOI: https://doi.org/10.1124/mol.62.4.901
Marco I. González
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Marcelo G. Kazanietz
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Michael B. Robinson
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Abstract

In previous studies, we have shown that activation of protein kinase C (PKC) rapidly (within minutes) increases the activity and cell surface expression of the glutamate transporter EAAC1 in two systems that endogenously express this transporter (C6 glioma cells and cocultures of neurons and astrocytes). However, the magnitude of the increase in activity is greater than the increase in cell surface expression. In addition, certain compounds completely block the increase in cell surface expression but only partially attenuate the increase in activity. We hypothesized that PKC increases EAAC1 activity by increasing cell surface expression and catalytic efficiency and that two different subtypes of PKC mediate these effects. To address these hypotheses, the PKC subtypes expressed by C6 glioma cells were identified. Of the PKC subtypes that are activated by phorbol esters, only PKCα, PKCδ, and PKCε were observed. Gö6976, a compound that blocks PKCα at concentrations that do not inhibit PKCδ or PKCε, partially inhibited the increase in uptake but completely abolished the increase in EAAC1 cell surface expression. The ‘Gö6976-insensitive’ increase in activity was not associated with a change in total transporter expression but was associated with an increase in the V max. Na+-dependent glycine transport was not increased, providing indirect evidence that the Gö6976-insensitive increase in activity was not caused by a change in the Na+electrochemical gradient required for activity. Finally, by down-regulating different subtypes of PKC, we found evidence that PKCε mediates the increase in EAAC1 activity that is independent of changes in cell surface expression and found further evidence that PKCα mediates the increase in cell surface expression. The potential relationship of the present work with a previously identified role for PKCα in certain forms of synaptic plasticity is discussed.

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Molecular Pharmacology: 62 (4)
Molecular Pharmacology
Vol. 62, Issue 4
1 Oct 2002
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Research ArticleArticle

Regulation of the Neuronal Glutamate Transporter Excitatory Amino Acid Carrier-1 (EAAC1) by Different Protein Kinase C Subtypes

Marco I. González, Marcelo G. Kazanietz and Michael B. Robinson
Molecular Pharmacology October 1, 2002, 62 (4) 901-910; DOI: https://doi.org/10.1124/mol.62.4.901

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Research ArticleArticle

Regulation of the Neuronal Glutamate Transporter Excitatory Amino Acid Carrier-1 (EAAC1) by Different Protein Kinase C Subtypes

Marco I. González, Marcelo G. Kazanietz and Michael B. Robinson
Molecular Pharmacology October 1, 2002, 62 (4) 901-910; DOI: https://doi.org/10.1124/mol.62.4.901
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