TY - JOUR
T1 - CaMKII Phosphorylation of TARPγ-8 Is a Mediator of LTP and Learning and Memory
AU - Park, Joongkyu
AU - Chávez, Andrés E.
AU - Mineur, Yann S.
AU - Morimoto-Tomita, Megumi
AU - Lutzu, Stefano
AU - Kim, Kwang S.
AU - Picciotto, Marina R.
AU - Castillo, Pablo E.
AU - Tomita, Susumu
N1 - Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/10/5
Y1 - 2016/10/5
N2 - Protein phosphorylation is an essential step for the expression of long-term potentiation (LTP), a long-lasting, activity-dependent strengthening of synaptic transmission widely regarded as a cellular mechanism underlying learning and memory. At the core of LTP is the synaptic insertion of AMPA receptors (AMPARs) triggered by the NMDA receptor-dependent activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). However, the CaMKII substrate that increases AMPAR-mediated transmission during LTP remains elusive. Here, we identify the hippocampus-enriched TARPγ-8, but not TARPγ-2/3/4, as a critical CaMKII substrate for LTP. We found that LTP induction increases TARPγ-8 phosphorylation, and that CaMKII-dependent enhancement of AMPAR-mediated transmission requires CaMKII phosphorylation sites of TARPγ-8. Moreover, LTP and memory formation, but not basal transmission, are significantly impaired in mice lacking CaMKII phosphorylation sites of TARPγ-8. Together, these findings demonstrate that TARPγ-8 is a crucial mediator of CaMKII-dependent LTP and therefore a molecular target that controls synaptic plasticity and associated cognitive functions.
AB - Protein phosphorylation is an essential step for the expression of long-term potentiation (LTP), a long-lasting, activity-dependent strengthening of synaptic transmission widely regarded as a cellular mechanism underlying learning and memory. At the core of LTP is the synaptic insertion of AMPA receptors (AMPARs) triggered by the NMDA receptor-dependent activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). However, the CaMKII substrate that increases AMPAR-mediated transmission during LTP remains elusive. Here, we identify the hippocampus-enriched TARPγ-8, but not TARPγ-2/3/4, as a critical CaMKII substrate for LTP. We found that LTP induction increases TARPγ-8 phosphorylation, and that CaMKII-dependent enhancement of AMPAR-mediated transmission requires CaMKII phosphorylation sites of TARPγ-8. Moreover, LTP and memory formation, but not basal transmission, are significantly impaired in mice lacking CaMKII phosphorylation sites of TARPγ-8. Together, these findings demonstrate that TARPγ-8 is a crucial mediator of CaMKII-dependent LTP and therefore a molecular target that controls synaptic plasticity and associated cognitive functions.
UR - http://www.scopus.com/inward/record.url?scp=84992688642&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84992688642&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2016.09.002
DO - 10.1016/j.neuron.2016.09.002
M3 - Article
C2 - 27667007
AN - SCOPUS:84992688642
SN - 0896-6273
VL - 92
SP - 75
EP - 83
JO - Neuron
JF - Neuron
IS - 1
ER -