English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/40040
Title: PKC Anchoring to GluR4 AMPA Receptor Subunit Modulates PKC-Driven Receptor Phosphorylation and Surface Expression
Authors: Gomes, André R.; Correia, Susana S.; Esteban, José A.; Duarte, Carlos B.; Carvalho, Ana Luisa
Keywords: AMPA receptors
Surface expression
Synaptic delivery
Issue Date: 8-Mar-2007
Publisher: John Wiley & Sons
Citation: Traffic - International Journal of Intracellular Transport 8(3):259-69 (2007)
Abstract: Changes in the synaptic content of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)–type glutamate receptors lead to synaptic efficacy modifications, involved in synaptic plasticity mechanisms believed to underlie learning and memory formation. Early in development, GluR4 is highly expressed in the hippocampus, and GluR4-containing AMPA receptors are inserted into synapses. During synapse maturation, the number of AMPA receptors at the synapse is dynamically regulated, and both addition and removal of receptors from postsynaptic sites occur through regulated mechanisms. GluR4 delivery to synapses in rat hippocampal slices was shown to require protein kinase A (PKA)–mediated phosphorylation of GluR4 at serine 842 (Ser842). Protein kinase C (PKC) can also phosphorylate Ser842, and we have shown that PKCγ can associate with GluR4. Here we show that activation of PKC in retina neurons, or in human embryonic kidney 293 cells cotransfected with GluR4 and PKCγ, increases GluR4 surface expression and Ser842 phosphorylation. Moreover, mutation of amino acids R821A, K825A and R826A at the GluR4 C-terminal, within the interacting region of GluR4 with PKCγ, abolishes the interaction between PKCγ and GluR4 and prevents the stimulatory effect of PKCγ on GluR4 Ser842 phosphorylation and surface expression. These data argue for a role of anchored PKCγ in Ser842 phosphorylation and targeting to the plasma membrane. The triple GluR4 mutant is, however, phosphorylated by PKA, and it is targeted to the synapse in CA1 hippocampal neurons in organotypic rat hippocampal slices. The present findings show that the interaction between PKCγ and GluR4 is specifically required to assure PKC-driven phosphorylation and surface membrane expression of GluR4.
Publisher version (URL): http://dx.doi.org/10.1111/j.1600-0854.2006.00521.x
URI: http://hdl.handle.net/10261/40040
DOI: 10.1111/j.1600-0854.2006.00521.x
ISSN: 1398-9219
Appears in Collections:(CBM) Artículos
Files in This Item:
There are no files associated with this item.
Show full item record

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.