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STIM2 regulates AMPA receptor trafficking and plasticity at hippocampal synapses

STIM2 regulates AMPA receptor trafficking and plasticity at hippocampal synapses

Yap, Kenrick An Fu, Shetty, Mahesh Shivarama, Garcia-Alvarez, Gisela, Lu, Bo, Alagappan, Durgadevi, Oh-Hora, Masatsugu, Sajikumar, Sreedharan and Fivaz, Marc ORCID: 0000-0003-1003-7934 (2016) STIM2 regulates AMPA receptor trafficking and plasticity at hippocampal synapses. Neurobiology of Learning and Memory, 138. pp. 54-61. ISSN 1074-7427 (doi:

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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.

Item Type: Article
Uncontrolled Keywords: Endoplasmic reticulum; Excitatory synapse; Plasticity; Memory; Long-term potentiation; Long-term depression; AMPA receptors
Faculty / School / Research Centre / Research Group: Faculty of Engineering & Science
Faculty of Education, Health & Human Sciences > School of Human Sciences (HUM)
Last Modified: 09 Oct 2021 04:45

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