RRC ID 61453
Author Kakizawa S, Kishimoto Y, Yamamoto S, Onga K, Yasuda K, Miyamoto Y, Watanabe M, Sakai R, Mori N.
Title Functional maintenance of calcium store by ShcB adaptor protein in cerebellar Purkinje cells.
Journal Sci Rep
Abstract Intracellular Ca2+ levels are changed by influx from extracellular medium and release from intracellular stores. In the central nervous systems, Ca2+ release is involved in various physiological events, such as neuronal excitability and transmitter release. Although stable Ca2+ release in response to stimulus is critical for proper functions of the nervous systems, regulatory mechanisms relating to Ca2+ 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 Ca2+ 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 Ca2+ release. Although the expression of Ca2+ release channels and morphology of Ca2+ store looked intact, content of intracellular Ca2+ store and activity of sarco/endoplasmic reticular Ca2+-ATPase (SERCA) were largely decreased in the ShcB-deficient cerebellum. Furthermore, when ShcB was ectopically expressed in the ShcB-KO PCs, the Ca2+ release and its SERCA-dependent component were restored. These data indicate that ShcB plays a key role in the functional maintenance of ER Ca2+ store in central neurons through regulation of SERCA activity.
Volume 10(1)
Pages 14475
Published 2020-9-2
DOI 10.1038/s41598-020-71414-y
PII 10.1038/s41598-020-71414-y
PMID 32879382
PMC PMC7468156
MeSH Animals Calcium / metabolism Calcium Signaling / genetics Cerebellum / metabolism* Cerebellum / pathology Endoplasmic Reticulum / genetics Humans Long-Term Synaptic Depression / genetics* Mice Mice, Knockout Motor Disorders / genetics Motor Disorders / physiopathology Neuronal Plasticity / genetics Purkinje Cells / metabolism Purkinje Cells / pathology Sarcoplasmic Reticulum Calcium-Transporting ATPases / genetics* Src Homology 2 Domain-Containing, Transforming Protein 2 / genetics* Synapses / genetics*
IF 3.998
DNA material CSII-CMV-MCS-IRES2-mRFP1 (RDB07918) CSII-CMV-mRFP1 (RDB06386) pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393)
Human and Animal Cells 293T(RCB2202)