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The Journal of Neuroscience, July 2, 2003, 23(13):5589-5593
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BRIEF COMMUNICATION
Phorbol Myristate Acetate-Dependent Interaction of Protein Kinase C and the Neuronal Glutamate Transporter EAAC1
Marco I. González,1,2
Peter G. Bannerman,1 and
Michael B. Robinson1,2
Departments of 1Pediatrics and
2Pharmacology, Children's Hospital of Philadelphia,
University of Pennsylvania, Philadelphia PA 19104-4318
Sodium-dependent transporters clear extracellular glutamate in the
mammalian CNS. Activation of protein kinase C (PKC) rapidly increases the
activity of the neuronal glutamate transporter EAAC1 (excitatory amino acid
carrier-1). This effect is associated with redistribution of EAAC1 to the cell
membrane and appears to be dependent on a particular PKC subtype, PKC .
In the present study, we sought to determine whether this specificity for
regulation of EAAC1 is associated with the formation of EAAC1–PKC
complexes. In C6 glioma cells, activation of PKC with phorbol 12-myristate
13-acetate (PMA) induced formation of EAAC1–PKC complexes but did
not induce formation of complexes with PKC , a PKC not thought to
regulate EAAC1. Formation of these complexes was blocked by inhibitors of PKC.
Confocal microscopy revealed that PMA caused EAAC1 and PKC to
colocalize in clusters at or near the cell surface. The EAAC1–PKC
complexes were also observed in rat brain synaptosomes, demonstrating that
this interaction is not restricted to C6 cells. These data demonstrate that
EAAC1 and PKC interact in a PKC-dependent manner that is associated
with EAAC1 redistribution. Although PKC activation has been implicated in the
regulation of many different neurotransmitter transporters, this study
provides the first example of an interaction between a neurotransmitter
transporter and PKC. PKC also forms complexes with GluR2 (glutamate
receptor subunit 2) and causes a reduction in the levels of GluR2-containing
AMPA receptors at the plasma membrane. Together, these data suggest that
PKC may simultaneously trigger the redistribution of EAAC1 and
glutamate receptors.
Key words: glutamate transporter; EAAC1; trafficking; PKC; phorbol ester; C6 glioma
Received Mar. 26, 2003;
revised May. 5, 2003;
accepted May. 7, 2003.
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