P2X-mediated AMPA receptor internalization and synaptic depression is controlled by two CaMKII phosphorylation sites on GluA1 in hippocampal neurons.
Sci Rep. 2016-09-14; 6(1):
Lire sur PubMed
1. Sci Rep. 2016 Sep 14;6:31836. doi: 10.1038/srep31836.
P2X-mediated AMPA receptor internalization and synaptic depression is controlled
by two CaMKII phosphorylation sites on GluA1 in hippocampal neurons.
Pougnet JT(1)(2), Compans B(3)(4), Martinez A(1)(2), Choquet D(3)(4)(5), Hosy
E(3)(4), Boué-Grabot E(1)(2).
(1)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000
(2)CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux,
(3)Univ. de Bordeaux, Institut Interdisciplinaire des Neurosciences, UMR 5297,
F-33000 Bordeaux, France.
(4)CNRS, Institut Interdisciplinaire des Neurosciences, UMR 5297, F-33000
(5)Bordeaux Imaging Center, UMS 3420-US4 CNRS, INSERM, Université de Bordeaux,
Plasticity at excitatory synapses can be induced either by synaptic release of
glutamate or the release of gliotransmitters such as ATP. Recently, we showed
that postsynaptic P2X2 receptors activated by ATP released from astrocytes
downregulate synaptic AMPAR, providing a novel mechanism by which glial cells
modulate synaptic activity. ATP- and lNMDA-induced depression in the CA1 region
of the hippocampus are additive, suggesting distinct molecular pathways. AMPARs
are homo-or hetero-tetramers composed of GluA1-A4. Here, we first show that
P2X2-mediated AMPAR inhibition is dependent on the subunit composition of AMPAR.
GluA3 homomers are insensitive and their presence in heteromers alters
P2X-mediated inhibition. Using a mutational approach, we demonstrate that the two
CaMKII phosphorylation sites S567 and S831 located in the cytoplasmic Loop1 and
C-terminal tail of GluA1 subunits, respectively, are critical for P2X2-mediated
AMPAR inhibition recorded from co-expressing Xenopus oocytes and removal of
surface AMPAR at synapses of hippocampal neurons imaged by the super-resolution
dSTORM technique. Finally, using phosphorylation site-specific antibodies, we
show that P2X-induced depression in hippocampal slices produces a
dephosphorylation of the GluA1 subunit at S567, contrary to NMDAR-mediated LTD.
These findings indicate that GluA1 phosphorylation of S567 and S831 is critical
for P2X2-mediated AMPAR internalization and ATP-driven synaptic depression.
PMID: 27624155 [Indexed for MEDLINE]