STIM1 is cleaved by calpain

Prins, Daniel; Michalak, Marek

doi:10.1016/j.febslet.2015.09.015

Cited by 13 publications

(16 citation statements)

References 27 publications

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“…To investigate the linking between calpain and ER stress, we examined the protein levels of SERCA2a [18], STIM1 [19] and junctophilin-2 [20], previously reported as targets of calpain. HFD induced a reduction in junctophilin-2 protein levels (Fig.…”

Section: Resultsmentioning

confidence: 99%

Disruption of calpain reduces lipotoxicity-induced cardiac injury by preventing endoplasmic reticulum stress

Zhang

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Diabetes and obesity are prevalent in westernized countries. In both conditions, excessive fatty acid uptake by cardiomyocytes induces cardiac lipotoxicity, an important mechanism contributing to diabetic cardiomyopathy. This study investigated the effect of calpain disruption on cardiac lipotoxicity. Cardiac-specific capns1 knockout mice and their wild-type littermates (male, age of 4 weeks) were fed a high fat diet (HFD) or normal diet for 20 weeks. HFD increased body weight, altered blood lipid profiles and impaired glucose tolerance comparably in both capns1 knockout mice and their wild-type littermates. Calpain activity, cardiomyocyte cross-sectional areas, collagen deposition and triglyceride were significantly increased in HFD-fed mouse hearts, and these were accompanied by myocardial dysfunction and up-regulation of hypertrophic and fibrotic collagen genes as well as pro-inflammatory cytokines. These effects of HFD were attenuated by disruption of calpain in capns1 knockout mice. Mechanistically, deletion of capns1 in HFD-fed mouse hearts and disruption of calpain with calpain inhibitor-III, silencing of capn1, or deletion of capns1 in palmitate-stimulated cardiomyocytes prevented endoplasmic reticulum stress, apoptosis, cleavage of caspase-12 and junctophilin-2, and pro-inflammatory cytokine expression. Pharmacological inhibition of endoplasmic reticulum stress diminished palmitate-induced apoptosis and pro-inflammatory cytokine expression in cardiomyocytes. In summary, disruption of calpain prevents lipotoxicity-induced apoptosis in cardiomyocytes and cardiac injury in mice fed a HFD. The role of calpain is mediated, at least partially, through endoplasmic reticulum stress. Thus, calpain/endoplasmic reticulum stress may represent a new mechanism and potential therapeutic targets for cardiac lipotoxicity.

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Section: Resultsmentioning

confidence: 99%

Disruption of calpain reduces lipotoxicity-induced cardiac injury by preventing endoplasmic reticulum stress

Zhang

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…Regulation of STIM1 abundance or loss of protein can affect other cellular processes. Cleavage of STIM1 by calpain and γ-secretase is associated with stress and Alzheimer’s disease, respectively (36, 37). Further, proteasome inhibition reduces SOCE and promotes autophagy-mediated degradation of STIM1/2 (38).…”

Section: Discussionmentioning

confidence: 99%

Radiation inhibits salivary gland function by promoting STIM1 cleavage by caspase-3 and loss of SOCE through a TRPM2-dependent pathway

et al. 2017

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Store-operated Ca2+ entry (SOCE) is critical for salivary gland fluid secretion. We report that radiation treatment caused persistent salivary gland dysfunction by activating a TRPM2-dependent mitochondrial pathway, leading to caspase-3–mediated cleavage of stromal interaction molecule 1 (STIM1) and loss of SOCE. After irradiation, acinar cells from the submandibular glands of TRPM2+/+, but not those from TRPM2−/− mice, displayed an increase in the concentrations of mitochondrial Ca2+ and reactive oxygen species, a decrease in mitochondrial membrane potential, and activation of caspase-3, which was associated with a sustained decrease in STIM1 abundance and attenuation of SOCE. In a salivary gland cell line, silencing the mitochondrial Ca2+ uniporter or caspase-3 or treatment with inhibitors of TRPM2 or caspase-3 prevented irradiation-induced loss of STIM1 and SOCE. Expression of exogenous STIM1 in the salivary glands of irradiated mice increased SOCE and fluid secretion. We suggest that targeting the mechanisms underlying the loss of STIM1 would be a potentially useful approach for preserving salivary gland function after radiation therapy.

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“…In this scenario, the abundance of functional ion channels and thus the macroscopic current density decrease with no influence per se on their individual biophysical properties. Examples are found for various types of ion channels including voltage-gated potassium channels (hERG) [16–18], acid-sensing ion channels (ASIC-1) [19], NMDA receptors (NR2A subunits) [20], the Store-Operated Calcium Entry (SOCE) machinery (STIM1) [21, 22], and chloride channels (CFTR) [23]. (See Table 1).…”

Section: Disabling Channel Activities By Proteolysismentioning

confidence: 99%

“…This process is termed store operated Ca 2+ entry (SOCE) [25]. Calpain, γ-secretase and casepase-3 can cleave STIM1 thus regulating SOCE [21, 22, 26]. The Michalak group reported that calpain dynamically regulated STIM1 turnover and consequently SOCE through proteolysis of STIM1 proteins in both basal and apoptotic conditions.…”

Section: Disabling Channel Activities By Proteolysismentioning

confidence: 99%

Differential regulation of ion channels function by proteolysis

Wang¹,

Yule²

2018

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Ion channels are pore-forming protein complexes in membranes that play essential roles in a diverse array of biological activities. Ion channel activity is strictly regulated at multiple levels and by numerous cellular events to selectively activate downstream effectors involved in specific biological activities. For example, ions, binding proteins, nucleotides, phosphorylation, the redox state, channel subunit composition have all been shown to regulate channel activity and subsequently allow channels to participate in distinct cellular events. While these forms of modulation are well documented and have been extensively reviewed, in this article, we will first review and summarize channel proteolysis as a novel and quite widespread mechanism for altering channel activity. We will then highlight the recent findings demonstrating that proteolysis profoundly alters Inositol 1,4,5 trisphosphate receptor activity, and then discuss its potential functional ramifications in various developmental and pathological conditions.

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STIM1 is cleaved by calpain

Cited by 13 publications

References 27 publications

Disruption of calpain reduces lipotoxicity-induced cardiac injury by preventing endoplasmic reticulum stress

Disruption of calpain reduces lipotoxicity-induced cardiac injury by preventing endoplasmic reticulum stress

Radiation inhibits salivary gland function by promoting STIM1 cleavage by caspase-3 and loss of SOCE through a TRPM2-dependent pathway

Differential regulation of ion channels function by proteolysis

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