Functional maintenance of calcium store by ShcB adaptor protein in cerebellar Purkinje cells

Intracellular Ca levels are changed by influx from extracellular medium and release from intracellular stores. In the central nervous systems, Ca release is involved in various physiological events, such as neuronal excitability and transmitter release. Although stable Ca release in response to stim...

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Bibliographic Details
Published in:Scientific reports 2020-09, Vol.10 (1), p.14475-14475, Article 14475
Main Authors: Kakizawa, Sho, Kishimoto, Yasushi, Yamamoto, Shinichiro, Onga, Kazuko, Yasuda, Kunihiko, Miyamoto, Yoshiaki, Watanabe, Masahiko, Sakai, Ryuichi, Mori, Nozomu
Format: Article
Language:English
Subjects:
Animals
Asparagine
Calcium - metabolism
Calcium Signaling - genetics
Cerebellum - metabolism
Cerebellum - pathology
Chromosome 4
Diarrhea
Endoplasmic Reticulum - genetics
Gastrointestinal diseases
Genomes
Genomics
Hexose
Humans
Long-Term Synaptic Depression - genetics
Mice
Mice, Knockout
Motor Disorders - genetics
Motor Disorders - physiopathology
Neuronal Plasticity - genetics
Nucleotide sequence
Probiotics
Proteomes
Purkinje Cells - metabolism
Purkinje Cells - pathology
Saccharomyces
Sarcoplasmic Reticulum Calcium-Transporting ATPases - genetics
Src Homology 2 Domain-Containing, Transforming Protein 2 - genetics
Synapses - genetics
Taxonomy
Wine
Yogurt
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Summary:Intracellular Ca levels are changed by influx from extracellular medium and release from intracellular stores. In the central nervous systems, Ca release is involved in various physiological events, such as neuronal excitability and transmitter release. Although stable Ca release in response to stimulus is critical for proper functions of the nervous systems, regulatory mechanisms relating to Ca release are not fully understood in central neurons. Here, we demonstrate that ShcB, an adaptor protein expressed in central neurons, has an essential role in functional maintenance of Ca store in cerebellar Purkinje cells (PCs). ShcB-knockout (KO) mice showed defects in cerebellar-dependent motor function and long-term depression (LTD) at cerebellar synapse. The reduced LTD was accompanied with an impairment of intracellular Ca release. Although the expression of Ca release channels and morphology of Ca store looked intact, content of intracellular Ca store and activity of sarco/endoplasmic reticular Ca -ATPase (SERCA) were largely decreased in the ShcB-deficient cerebellum. Furthermore, when ShcB was ectopically expressed in the ShcB-KO PCs, the Ca release and its SERCA-dependent component were restored. These data indicate that ShcB plays a key role in the functional maintenance of ER Ca store in central neurons through regulation of SERCA activity.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-71414-y