STIM1 controls neuronal Ca²⁺ signaling, mGluR1-dependent synaptic transmission, and cerebellar motor behavior
Autor: | Hartmann, Jana, Karl, Rosa M, Misgeld, Thomas, Konnerth, Arthur, Alexander, Ryan P D, Adelsberger, Helmuth, Brill, Monika S, Rühlmann, Charlotta, Ansel, Anna, Sakimura, Kenji, Baba, Yoshihiro, Kurosaki, Tomohiro |
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Rok vydání: | 2014 |
Předmět: |
metabotropic glutamate receptor type 1
physiology [Excitatory Postsynaptic Potentials] Mice Transgenic Stim1 protein mouse Motor Activity Receptors Metabotropic Glutamate Synaptic Transmission Mice physiology [Membrane Glycoproteins] Organ Culture Techniques Cerebellum Animals ddc:610 Calcium Signaling Stromal Interaction Molecule 1 physiology [Receptors Metabotropic Glutamate] Mice Knockout Neurons Membrane Glycoproteins physiology [Cerebellum] Excitatory Postsynaptic Potentials physiology [Neurons] cytology [Cerebellum] physiology [Motor Activity] physiology [Synaptic Transmission] physiology [Calcium Signaling] Calcium Channels |
Zdroj: | Neuron 82(3), 635-644 (2014). doi:10.1016/j.neuron.2014.03.027 |
ISSN: | 1097-4199 |
Popis: | 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. |
Databáze: | OpenAIRE |
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