Mechanism of Ca2+/calmodulin-dependent kinase II regulation of AMPA receptor gating
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Mechanism of Ca2+/calmodulin-dependent kinase II regulation of AMPA receptor gating. / Kristensen, Anders Skov; Jenkins, Meagan A; Banke, Tue G; Schousboe, Arne; Makino, Yuichi; Johnson, Richard C; Huganir, Richard; Traynelis, Stephen F.
In: Nature Neuroscience, Vol. 14, No. 6, 01.06.2011, p. 727-735.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Mechanism of Ca2+/calmodulin-dependent kinase II regulation of AMPA receptor gating
AU - Kristensen, Anders Skov
AU - Jenkins, Meagan A
AU - Banke, Tue G
AU - Schousboe, Arne
AU - Makino, Yuichi
AU - Johnson, Richard C
AU - Huganir, Richard
AU - Traynelis, Stephen F
PY - 2011/6/1
Y1 - 2011/6/1
N2 - The function, trafficking and synaptic signaling of AMPA receptors are tightly regulated by phosphorylation. Ca(2+)/calmodulin-dependent kinase II (CaMKII) phosphorylates the GluA1 AMPA receptor subunit at Ser831 to increase single-channel conductance. We show that CaMKII increases the conductance of native heteromeric AMPA receptors in mouse hippocampal neurons through phosphorylation of Ser831. In addition, co-expression of transmembrane AMPA receptor regulatory proteins (TARPs) with recombinant receptors is required for phospho-Ser831 to increase conductance of heteromeric GluA1-GluA2 receptors. Finally, phosphorylation of Ser831 increases the efficiency with which each subunit can activate, independent of agonist efficacy, thereby increasing the likelihood that more receptor subunits will be simultaneously activated during gating. This underlies the observation that phospho-Ser831 increases the frequency of openings to larger conductances rather than altering unitary conductance. Together, these findings suggest that CaMKII phosphorylation of GluA1-Ser831 decreases the activation energy for an intrasubunit conformational change that regulates the conductance of the receptor when the channel pore opens.
AB - The function, trafficking and synaptic signaling of AMPA receptors are tightly regulated by phosphorylation. Ca(2+)/calmodulin-dependent kinase II (CaMKII) phosphorylates the GluA1 AMPA receptor subunit at Ser831 to increase single-channel conductance. We show that CaMKII increases the conductance of native heteromeric AMPA receptors in mouse hippocampal neurons through phosphorylation of Ser831. In addition, co-expression of transmembrane AMPA receptor regulatory proteins (TARPs) with recombinant receptors is required for phospho-Ser831 to increase conductance of heteromeric GluA1-GluA2 receptors. Finally, phosphorylation of Ser831 increases the efficiency with which each subunit can activate, independent of agonist efficacy, thereby increasing the likelihood that more receptor subunits will be simultaneously activated during gating. This underlies the observation that phospho-Ser831 increases the frequency of openings to larger conductances rather than altering unitary conductance. Together, these findings suggest that CaMKII phosphorylation of GluA1-Ser831 decreases the activation energy for an intrasubunit conformational change that regulates the conductance of the receptor when the channel pore opens.
KW - Former Faculty of Pharmaceutical Sciences
U2 - 10.1038/nn.2804
DO - 10.1038/nn.2804
M3 - Journal article
C2 - 21516102
VL - 14
SP - 727
EP - 735
JO - Nature Neuroscience
JF - Nature Neuroscience
SN - 1097-6256
IS - 6
ER -
ID: 35413307