title: STIM1 controls neuronal Ca²⁺ signaling, mGluR1-dependent synaptic transmission, and cerebellar motor behavior.
abstract: In central mammalian neurons, activation of metabotropic glutamate receptor type1 (mGluR1) evokes a complex synaptic response consisting of IP3 receptor-dependent Ca(2+) release from internal Ca(2+) stores and a slow depolarizing potential involving TRPC3 channels. It is largely unclear how mGluR1 is linked to its downstream effectors. Here, we explored the role of stromal interaction molecule 1 (STIM1) in regulating neuronal Ca(2+) signaling and mGluR1-dependent synaptic transmission. By analyzing mouse cerebellar Purkinje neurons, we demonstrate that STIM1 is an essential regulator of the Ca(2+) level in neuronal endoplasmic reticulum Ca(2+) stores. Both mGluR1-dependent synaptic potentials and IP3 receptor-dependent Ca(2+) signals are strongly attenuated in the absence of STIM1. Furthermore, the Purkinje neuron-specific deletion of Stim1 causes impairments in cerebellar motor behavior. Together, our results demonstrate that in the mammalian nervous system STIM1 is a key regulator of intracellular Ca(2+) signaling, metabotropic glutamate receptor-dependent synaptic transmission, and motor coordination.
authors.affiliation: Institute of Neuroscience, Technical University Munich, Biedersteiner Straße 29, 80802 Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Biedersteiner Straße 29, 80802 Munich, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Hartmann
authors.affiliation: Institute of Neuroscience, Technical University Munich, Biedersteiner Straße 29, 80802 Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Biedersteiner Straße 29, 80802 Munich, Germany.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Karl
authors.affiliation: Institute of Neuroscience, Technical University Munich, Biedersteiner Straße 29, 80802 Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Biedersteiner Straße 29, 80802 Munich, Germany.
authors.forename: Ryan P D
authors.initials: RP
authors.lastname: Alexander
authors.affiliation: Institute of Neuroscience, Technical University Munich, Biedersteiner Straße 29, 80802 Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Biedersteiner Straße 29, 80802 Munich, Germany.
authors.forename: Helmuth
authors.initials: H
authors.lastname: Adelsberger
authors.affiliation: Munich Cluster for Systems Neurology (SyNergy), Biedersteiner Straße 29, 80802 Munich, Germany; Center for Integrated Protein Sciences (CIPSM), Biedersteiner Straße 29, 80802 Munich, Germany; Chair for Biomolecular Sensors and German Center for Neurodegenerative Diseases (DZNE), Technical University Munich, Biedersteiner Straße 29, 80802 Munich, Germany.
authors.forename: Monika S
authors.initials: MS
authors.lastname: Brill
authors.affiliation: Institute of Neuroscience, Technical University Munich, Biedersteiner Straße 29, 80802 Munich, Germany.
authors.forename: Charlotta
authors.initials: C
authors.lastname: Rühlmann
authors.affiliation: Institute of Neuroscience, Technical University Munich, Biedersteiner Straße 29, 80802 Munich, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Ansel
authors.affiliation: Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakimura
authors.affiliation: Immunology Frontier Research Center, Osaka University, 9F Integrated Life Science Building, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Baba
authors.affiliation: Immunology Frontier Research Center, Osaka University, 9F Integrated Life Science Building, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kurosaki
authors.affiliation: Munich Cluster for Systems Neurology (SyNergy), Biedersteiner Straße 29, 80802 Munich, Germany; Center for Integrated Protein Sciences (CIPSM), Biedersteiner Straße 29, 80802 Munich, Germany; Chair for Biomolecular Sensors and German Center for Neurodegenerative Diseases (DZNE), Technical University Munich, Biedersteiner Straße 29, 80802 Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Misgeld
authors.affiliation: Institute of Neuroscience, Technical University Munich, Biedersteiner Straße 29, 80802 Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Biedersteiner Straße 29, 80802 Munich, Germany. Electronic address: arthur.konnerth@lrz.tum.de.
authors.forename: Arthur
authors.initials: A
authors.lastname: Konnerth
mesh_terms: D000818:Animals; D015220:Calcium Channels; D020013:Calcium Signaling / Q000502:physiology*; D002531:Cerebellum / Q000166:cytology / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D009924:Organ Culture Techniques; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D000071737:Stromal Interaction Molecule 1; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D008562:Membrane Glycoproteins; D018094:Receptors, Metabotropic Glutamate; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; C104077:metabotropic glutamate receptor type 1