STIM1 Controls Neuronal Ca2+ Signaling, mGluR1-Dependent Synaptic Transmission, and Cerebellar Motor Behavior

Jana Hartmann, Rosa M. Karl, Ryan P.D. Alexander, Helmuth Adelsberger, Monika S. Brill, Charlotta Rühlmann, Anna Ansel, Kenji Sakimura, Yoshihiro Baba, Tomohiro Kurosaki, Thomas Misgeld, Arthur Konnerth

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

In central mammalian neurons, activation of metabotropic glutamate receptor type1 (mGluR1) evokes a complex synaptic response consisting of IP3 receptor-dependent Ca2+ release from internal Ca2+ 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 Ca2+ signaling and mGluR1-dependent synaptic transmission. By analyzing mouse cerebellar Purkinje neurons, we demonstrate that STIM1 is an essential regulator of the Ca2+ level in neuronal endoplasmic reticulum Ca2+ stores. Both mGluR1-dependent synaptic potentials and IP3 receptor-dependent Ca2+ 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 Ca2+ signaling, metabotropic glutamate receptor-dependent synaptic transmission, and motor coordination.

Original languageEnglish
Pages (from-to)635-644
Number of pages10
JournalNeuron
Volume82
Issue number3
DOIs
Publication statusPublished - May 7 2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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