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
Rok vydání: 2014
Předmět:
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