| 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
|
| Resource |
| 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) |
