TY - JOUR
T1 - STIM2 regulates AMPA receptor trafficking and plasticity at hippocampal synapses
AU - Yap, Kenrick An Fu
AU - Shetty, Mahesh Shivarama
AU - Garcia-Alvarez, Gisela
AU - Lu, Bo
AU - Alagappan, Durgadevi
AU - Oh-Hora, Masatsugu
AU - Sajikumar, Sreedharan
AU - Fivaz, Marc
N1 - Funding Information:
We thank Tan Li Ting for excellent technical assistance. This work was supported by grants to MF from the Singapore Ministry of Education Academic Research Fund (MOE2011-T2-1-107), and the Agency for Science, Technology and Research (Astar/JJSI 13/1/24/26/011). SS is supported by the National Medical Research Council, Singapore Technology and Research (NMRC-CBRG-0041/2013).
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2017/2/1
Y1 - 2017/2/1
N2 - STIM2 is an integral membrane protein of the endoplasmic reticulum (ER) that regulates the activity of plasma membrane (PM) channels at ER-PM contact sites. Recent studies show that STIM2 promotes spine maturation and surface expression of the AMPA receptor (AMPAR) subunit GluA1, hinting at a probable role in synaptic plasticity. Here, we used a Stim2 cKO mouse to explore the function of STIM2 in Long-Term Potentiation (LTP) and Depression (LTD), two widely-studied models of synaptic plasticity implicated in information storage. We found that STIM2 is required for the stable expression of both LTP and LTD at CA3-CA1 hippocampal synapses. Altered plasticity in Stim2 cKO mice is associated with subtle alterations in the shape and density of dendritic spines in CA1 neurons. Further, surface delivery of GluA1 in response to LTP-inducing chemical manipulations was markedly reduced in excitatory neurons derived from Stim2 cKO mice. GluA1 endocytosis following chemically-induced LTD was also impaired in Stim2 cKO neurons. We conclude that STIM2 facilitates synaptic delivery and removal of AMPARs and regulates activity-dependent changes in synaptic strength through a unique mode of communication between the ER and the synapse.
AB - STIM2 is an integral membrane protein of the endoplasmic reticulum (ER) that regulates the activity of plasma membrane (PM) channels at ER-PM contact sites. Recent studies show that STIM2 promotes spine maturation and surface expression of the AMPA receptor (AMPAR) subunit GluA1, hinting at a probable role in synaptic plasticity. Here, we used a Stim2 cKO mouse to explore the function of STIM2 in Long-Term Potentiation (LTP) and Depression (LTD), two widely-studied models of synaptic plasticity implicated in information storage. We found that STIM2 is required for the stable expression of both LTP and LTD at CA3-CA1 hippocampal synapses. Altered plasticity in Stim2 cKO mice is associated with subtle alterations in the shape and density of dendritic spines in CA1 neurons. Further, surface delivery of GluA1 in response to LTP-inducing chemical manipulations was markedly reduced in excitatory neurons derived from Stim2 cKO mice. GluA1 endocytosis following chemically-induced LTD was also impaired in Stim2 cKO neurons. We conclude that STIM2 facilitates synaptic delivery and removal of AMPARs and regulates activity-dependent changes in synaptic strength through a unique mode of communication between the ER and the synapse.
UR - http://www.scopus.com/inward/record.url?scp=84994364990&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84994364990&partnerID=8YFLogxK
U2 - 10.1016/j.nlm.2016.08.007
DO - 10.1016/j.nlm.2016.08.007
M3 - Article
C2 - 27544849
AN - SCOPUS:84994364990
SN - 1074-7427
VL - 138
SP - 54
EP - 61
JO - Neurobiology of Learning and Memory
JF - Neurobiology of Learning and Memory
ER -