PMID- 12843260
OWN - NLM
STAT- MEDLINE
DCOM- 20030814
LR  - 20231013
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 23
IP  - 13
DP  - 2003 Jul 2
TI  - Phorbol myristate acetate-dependent interaction of protein kinase Calpha and the 
      neuronal glutamate transporter EAAC1.
PG  - 5589-93
AB  - 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, PKCalpha. In the present 
      study, we sought to determine whether this specificity for regulation of EAAC1 is 
      associated with the formation of EAAC1-PKCalpha complexes. In C6 glioma cells, 
      activation of PKC with phorbol 12-myristate 13-acetate (PMA) induced formation of 
      EAAC1-PKCalpha complexes but did not induce formation of complexes with PKCdelta, 
      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 
      PKCalpha to colocalize in clusters at or near the cell surface. The 
      EAAC1-PKCalpha complexes were also observed in rat brain synaptosomes, 
      demonstrating that this interaction is not restricted to C6 cells. These data 
      demonstrate that EAAC1 and PKCalpha 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. PKCalpha 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 PKCalpha may 
      simultaneously trigger the redistribution of EAAC1 and glutamate receptors.
FAU - Gonzalez, Marco I
AU  - Gonzalez MI
AD  - Department of Pediatrics, Children's Hospital of Philadelphia, University of 
      Pennsylvania, Philadelphia 19104-4318, USA.
FAU - Bannerman, Peter G
AU  - Bannerman PG
FAU - Robinson, Michael B
AU  - Robinson MB
LA  - eng
GR  - R01 NS029868/NS/NINDS NIH HHS/United States
GR  - R01 NS039011/NS/NINDS NIH HHS/United States
GR  - NS29868/NS/NINDS NIH HHS/United States
GR  - NS39011/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Amino Acid Transport System X-AG)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Excitatory Amino Acid Transporter 3)
RN  - 0 (Glutamate Plasma Membrane Transport Proteins)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Slc1a1 protein, rat)
RN  - 0 (Symporters)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.13 (Protein Kinase C-alpha)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Amino Acid Transport System X-AG/*metabolism
MH  - Animals
MH  - Brain/metabolism
MH  - Cells, Cultured
MH  - Enzyme Activation/drug effects/physiology
MH  - Enzyme Inhibitors/pharmacology
MH  - Excitatory Amino Acid Transporter 3
MH  - Glioma/drug therapy/*metabolism
MH  - Glutamate Plasma Membrane Transport Proteins
MH  - Macromolecular Substances
MH  - Neurons/*metabolism
MH  - Protein Kinase C/antagonists & inhibitors/*metabolism
MH  - Protein Kinase C-alpha
MH  - Rats
MH  - Symporters/*metabolism
MH  - Synaptosomes/chemistry/metabolism
MH  - Tetradecanoylphorbol Acetate/*pharmacology
PMC - PMC6741220
EDAT- 2003/07/05 05:00
MHDA- 2003/08/15 05:00
PMCR- 2004/01/02
CRDT- 2003/07/05 05:00
PHST- 2003/07/05 05:00 [pubmed]
PHST- 2003/08/15 05:00 [medline]
PHST- 2003/07/05 05:00 [entrez]
PHST- 2004/01/02 00:00 [pmc-release]
AID - 23/13/5589 [pii]
AID - 10.1523/JNEUROSCI.23-13-05589.2003 [doi]
PST - ppublish
SO  - J Neurosci. 2003 Jul 2;23(13):5589-93. doi: 10.1523/JNEUROSCI.23-13-05589.2003.