title: STIM2 regulates AMPA receptor trafficking and plasticity at hippocampal synapses.
abstract: 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.
authors.affiliation: Duke-NUS Medical School, programme in Neuroscience and Behavioral Disorders, Singapore 169857, Singapore.
authors.forename: Kenrick An Fu
authors.initials: KA
authors.lastname: Yap
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Mahesh Shivarama
authors.initials: MS
authors.lastname: Shetty
authors.affiliation: Duke-NUS Medical School, programme in Neuroscience and Behavioral Disorders, Singapore 169857, Singapore.
authors.forename: Gisela
authors.initials: G
authors.lastname: Garcia-Alvarez
authors.affiliation: Duke-NUS Medical School, programme in Neuroscience and Behavioral Disorders, Singapore 169857, Singapore.
authors.forename: Bo
authors.initials: B
authors.lastname: Lu
authors.affiliation: Duke-NUS Medical School, programme in Neuroscience and Behavioral Disorders, Singapore 169857, Singapore.
authors.forename: Durgadevi
authors.initials: D
authors.lastname: Alagappan
authors.affiliation: Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Oh-Hora
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: phssks@nus.edu.sg.
authors.forename: Sreedharan
authors.initials: S
authors.lastname: Sajikumar
authors.affiliation: Duke-NUS Medical School, programme in Neuroscience and Behavioral Disorders, Singapore 169857, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: marc.fivaz@duke-nus.edu.sg.
authors.forename: Marc
authors.initials: M
authors.lastname: Fivaz
mesh_terms: D000818:Animals; D048430:Cell Shape / Q000502:physiology; D049229:Dendritic Spines / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology*; D018091:Receptors, AMPA / Q000378:metabolism*; D000071738:Stromal Interaction Molecule 2 / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
chemical_list: D018091:Receptors, AMPA; C525024:Stim2 protein, mouse; D000071738:Stromal Interaction Molecule 2
keywords: AMPA receptors; Endoplasmic reticulum; Excitatory synapse; Long-term depression; Long-term potentiation; Memory; Plasticity