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Ttm50 facilitates calpain activation by anchoring it to calcium stores and increasing its sensitivity to calcium
by
Zhang, Yong Q.
, Metwally, Elsayed
, Wang, Qifu
, Zhao, Guoli
in
13/106
/ 13/51
/ 14/19
/ 42/89
/ 631/136
/ 631/80/474
/ 64/24
/ 82/1
/ 82/29
/ 82/83
/ 9/10
/ Animals
/ Biomedical and Life Sciences
/ Calcium
/ Calcium (intracellular)
/ Calcium (reticular)
/ Calcium - metabolism
/ Calpain
/ Calpain - chemistry
/ Calpain - metabolism
/ Cell Biology
/ Down-Regulation
/ Drosophila - metabolism
/ Drosophila Proteins - antagonists & inhibitors
/ Drosophila Proteins - chemistry
/ Drosophila Proteins - genetics
/ Drosophila Proteins - metabolism
/ Endoplasmic reticulum
/ Endoplasmic Reticulum - metabolism
/ Glutamate receptors
/ Golgi apparatus
/ Golgi Apparatus - metabolism
/ HEK293 Cells
/ Humans
/ Life Sciences
/ Localization
/ Mitochondria
/ Mitochondrial Proteins - antagonists & inhibitors
/ Mitochondrial Proteins - genetics
/ Mitochondrial Proteins - metabolism
/ Physiology
/ Protein Binding
/ Proteolysis
/ Receptors, Ionotropic Glutamate - genetics
/ Receptors, Ionotropic Glutamate - metabolism
/ RNA Interference
/ RNA, Small Interfering - metabolism
/ Sensitivity
2021
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Ttm50 facilitates calpain activation by anchoring it to calcium stores and increasing its sensitivity to calcium
by
Zhang, Yong Q.
, Metwally, Elsayed
, Wang, Qifu
, Zhao, Guoli
in
13/106
/ 13/51
/ 14/19
/ 42/89
/ 631/136
/ 631/80/474
/ 64/24
/ 82/1
/ 82/29
/ 82/83
/ 9/10
/ Animals
/ Biomedical and Life Sciences
/ Calcium
/ Calcium (intracellular)
/ Calcium (reticular)
/ Calcium - metabolism
/ Calpain
/ Calpain - chemistry
/ Calpain - metabolism
/ Cell Biology
/ Down-Regulation
/ Drosophila - metabolism
/ Drosophila Proteins - antagonists & inhibitors
/ Drosophila Proteins - chemistry
/ Drosophila Proteins - genetics
/ Drosophila Proteins - metabolism
/ Endoplasmic reticulum
/ Endoplasmic Reticulum - metabolism
/ Glutamate receptors
/ Golgi apparatus
/ Golgi Apparatus - metabolism
/ HEK293 Cells
/ Humans
/ Life Sciences
/ Localization
/ Mitochondria
/ Mitochondrial Proteins - antagonists & inhibitors
/ Mitochondrial Proteins - genetics
/ Mitochondrial Proteins - metabolism
/ Physiology
/ Protein Binding
/ Proteolysis
/ Receptors, Ionotropic Glutamate - genetics
/ Receptors, Ionotropic Glutamate - metabolism
/ RNA Interference
/ RNA, Small Interfering - metabolism
/ Sensitivity
2021
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Ttm50 facilitates calpain activation by anchoring it to calcium stores and increasing its sensitivity to calcium
by
Zhang, Yong Q.
, Metwally, Elsayed
, Wang, Qifu
, Zhao, Guoli
in
13/106
/ 13/51
/ 14/19
/ 42/89
/ 631/136
/ 631/80/474
/ 64/24
/ 82/1
/ 82/29
/ 82/83
/ 9/10
/ Animals
/ Biomedical and Life Sciences
/ Calcium
/ Calcium (intracellular)
/ Calcium (reticular)
/ Calcium - metabolism
/ Calpain
/ Calpain - chemistry
/ Calpain - metabolism
/ Cell Biology
/ Down-Regulation
/ Drosophila - metabolism
/ Drosophila Proteins - antagonists & inhibitors
/ Drosophila Proteins - chemistry
/ Drosophila Proteins - genetics
/ Drosophila Proteins - metabolism
/ Endoplasmic reticulum
/ Endoplasmic Reticulum - metabolism
/ Glutamate receptors
/ Golgi apparatus
/ Golgi Apparatus - metabolism
/ HEK293 Cells
/ Humans
/ Life Sciences
/ Localization
/ Mitochondria
/ Mitochondrial Proteins - antagonists & inhibitors
/ Mitochondrial Proteins - genetics
/ Mitochondrial Proteins - metabolism
/ Physiology
/ Protein Binding
/ Proteolysis
/ Receptors, Ionotropic Glutamate - genetics
/ Receptors, Ionotropic Glutamate - metabolism
/ RNA Interference
/ RNA, Small Interfering - metabolism
/ Sensitivity
2021
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Ttm50 facilitates calpain activation by anchoring it to calcium stores and increasing its sensitivity to calcium
Journal Article
Ttm50 facilitates calpain activation by anchoring it to calcium stores and increasing its sensitivity to calcium
2021
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Overview
Calcium-dependent proteolytic calpains are implicated in a variety of physiological processes, as well as pathologies associated with calcium overload. However, the mechanism by which calpain is activated remains elusive since intracellular calcium levels under physiological conditions do not reach the high concentration range required to trigger calpain activation. From a candidate screening using the abundance of the calpain target glutamate receptor GluRIIA at the
Drosophila
neuromuscular junction as a readout, we uncovered that calpain activity was inhibited upon knockdown of Ttm50, a subunit of the Tim23 complex known to be involved in the import of proteins across the mitochondrial inner membrane. Unexpectedly, Ttm50 and calpain are co-localized at calcium stores Golgi and endoplasmic reticulum (ER), and Ttm50 interacts with calpain via its C-terminal domain. This interaction is required for calpain localization at Golgi/ER, and increases calcium sensitivity of calpain by roughly an order of magnitude. Our findings reveal the regulation of calpain activation by Ttm50, and shed new light on calpain-associated pathologies.
Publisher
Springer Singapore,Nature Publishing Group
Subject
/ 13/51
/ 14/19
/ 42/89
/ 631/136
/ 64/24
/ 82/1
/ 82/29
/ 82/83
/ 9/10
/ Animals
/ Biomedical and Life Sciences
/ Calcium
/ Calpain
/ Drosophila Proteins - antagonists & inhibitors
/ Drosophila Proteins - chemistry
/ Drosophila Proteins - genetics
/ Drosophila Proteins - metabolism
/ Endoplasmic Reticulum - metabolism
/ Golgi Apparatus - metabolism
/ Humans
/ Mitochondrial Proteins - antagonists & inhibitors
/ Mitochondrial Proteins - genetics
/ Mitochondrial Proteins - metabolism
/ Receptors, Ionotropic Glutamate - genetics
/ Receptors, Ionotropic Glutamate - metabolism
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