TY - JOUR
T1 - PKA-GluA1 coupling via AKAP5 controls AMPA receptor phosphorylation and cell-surface targeting during bidirectional homeostatic plasticity
AU - Diering, Graham H.
AU - Gustina, Ahleah S.
AU - Huganir, Richard L.
N1 - Funding Information:
We thank members of the Huganir lab for helpful discussion. A-kinase activity reporter 4 (AKAR4) was a generous gift from Dr. Jin Zhang, Johns Hopkins University. G.H.D. is a recipient of a Canadian Institute for Health Research postdoctoral fellowship award. This research was funded by the Howard Hughes Medical Institute and a grant from NINDS (NS 036715). Under a licensing agreement between Millipore Corporation and The Johns Hopkins University, R.L.H. is entitled to a share of royalties received by the University on sales of products described in this article. R.L.H. is a paid consultant to Millipore Corporation. The terms of this arrangement are being managed by The Johns Hopkins University in accordance with its conflict-of-interest policies.
Publisher Copyright:
© 2014 Elsevier Inc.
PY - 2014/11/19
Y1 - 2014/11/19
N2 - Bidirectional synaptic plasticity occurs locally at individual synapses during long-term potentiation (LTP) or long-term depression (LTD), or globally during homeostatic scaling. LTP, LTD, and homeostatic scaling alter synaptic strength through changes inpostsynaptic AMPA-type glutamate receptors (AMPARs), suggesting the existence of overlapping molecular mechanisms. Phosphorylation controls AMPAR trafficking during LTP/LTD. We addressed the role of AMPAR phosphorylation during homeostatic scaling. We observed bidirectional changes of the levels of phosphorylated GluA1 S845 during scaling, resulting from a loss of protein kinase A (PKA) from synapses during scaling down and enhanced activity of PKA in synapses during scaling up. Increased phosphorylation of S845 drove scaling up, while a knockin mutation of S845, or knockdown of the scaffold AKAP5, blocked scaling up. Finally, we show that AMPARs scale differentially based on their phosphorylation status at S845. These results show that rearrangement in PKA signaling controls AMPAR phosphorylation and surface targeting during homeostatic plasticity.
AB - Bidirectional synaptic plasticity occurs locally at individual synapses during long-term potentiation (LTP) or long-term depression (LTD), or globally during homeostatic scaling. LTP, LTD, and homeostatic scaling alter synaptic strength through changes inpostsynaptic AMPA-type glutamate receptors (AMPARs), suggesting the existence of overlapping molecular mechanisms. Phosphorylation controls AMPAR trafficking during LTP/LTD. We addressed the role of AMPAR phosphorylation during homeostatic scaling. We observed bidirectional changes of the levels of phosphorylated GluA1 S845 during scaling, resulting from a loss of protein kinase A (PKA) from synapses during scaling down and enhanced activity of PKA in synapses during scaling up. Increased phosphorylation of S845 drove scaling up, while a knockin mutation of S845, or knockdown of the scaffold AKAP5, blocked scaling up. Finally, we show that AMPARs scale differentially based on their phosphorylation status at S845. These results show that rearrangement in PKA signaling controls AMPAR phosphorylation and surface targeting during homeostatic plasticity.
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U2 - 10.1016/j.neuron.2014.09.024
DO - 10.1016/j.neuron.2014.09.024
M3 - Article
C2 - 25451194
AN - SCOPUS:84918787946
SN - 0896-6273
VL - 84
SP - 790
EP - 805
JO - Neuron
JF - Neuron
IS - 4
ER -