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Neuron. 2014 May 7;82(3):635-44. doi: 10.1016/j.neuron.2014.03.027.

STIM1 controls neuronal Ca²⁺ signaling, mGluR1-dependent synaptic transmission, and cerebellar motor behavior.

Author information

1
Institute of Neuroscience, Technical University Munich, Biedersteiner Straße 29, 80802 Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Biedersteiner Straße 29, 80802 Munich, Germany.
2
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.
3
Institute of Neuroscience, Technical University Munich, Biedersteiner Straße 29, 80802 Munich, Germany.
4
Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
5
Immunology Frontier Research Center, Osaka University, 9F Integrated Life Science Building, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
6
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.

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.

PMID:
24811382
DOI:
10.1016/j.neuron.2014.03.027
[Indexed for MEDLINE]
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