scholarly journals Calsequestrin 1 Is an Active Partner of Stromal Interaction Molecule 2 in Skeletal Muscle

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2821
Author(s):  
Seung Yeon Jeong ◽  
Mi Ri Oh ◽  
Jun Hee Choi ◽  
Jin Seok Woo ◽  
Eun Hui Lee
Keyword(s):  
Skeletal Muscle ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transmission Electron ◽  
Skeletal Muscle Contraction ◽  
Skeletal Myotubes ◽  
Functional Relevance ◽  
Transient Receptor ◽  
Canonical Type ◽  
Related Proteins

Calsequestrin 1 (CASQ1) in skeletal muscle buffers and senses Ca2+ in the sarcoplasmic reticulum (SR). CASQ1 also regulates store-operated Ca2+ entry (SOCE) by binding to stromal interaction molecule 1 (STIM1). Abnormal SOCE and/or abnormal expression or mutations in CASQ1, STIM1, or STIM2 are associated with human skeletal, cardiac, or smooth muscle diseases. However, the functional relevance of CASQ1 along with STIM2 has not been studied in any tissue, including skeletal muscle. First, in the present study, it was found by biochemical approaches that CASQ1 is bound to STIM2 via its 92 N-terminal amino acids (C1 region). Next, to examine the functional relevance of the CASQ1-STIM2 interaction in skeletal muscle, the full-length wild-type CASQ1 or the C1 region was expressed in mouse primary skeletal myotubes, and the myotubes were examined using single-myotube Ca2+ imaging experiments and transmission electron microscopy observations. The CASQ1-STIM2 interaction via the C1 region decreased SOCE, increased intracellular Ca2+ release for skeletal muscle contraction, and changed intracellular Ca2+ distributions (high Ca2+ in the SR and low Ca2+ in the cytosol were observed). Furthermore, the C1 region itself (which lacks Ca2+-buffering ability but has STIM2-binding ability) decreased the expression of Ca2+-related proteins (canonical-type transient receptor potential cation channel type 6 and calmodulin 1) and induced mitochondrial shape abnormalities. Therefore, in skeletal muscle, CASQ1 plays active roles in Ca2+ movement and distribution by interacting with STIM2 as well as Ca2+ sensing and buffering.

S165F mutation of junctophilin 2 affects Ca2+ signalling in skeletal muscle

2010 ◽  
Vol 427 (1) ◽  
pp. 125-134 ◽  
Author(s):  
Jin Seok Woo ◽  
Ji-Hye Hwang ◽  
Jae-Kyun Ko ◽  
Noah Weisleder ◽  
Do Han Kim ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Dominant Negative ◽  
Skeletal Muscle Function ◽  
Primary Mouse ◽  
Pkc Protein Kinase C ◽  
Skeletal Myotubes ◽  
Transient Receptor ◽  
Canonical Type

JPs (junctophilins) contribute to the formation of junctional membrane complexes in muscle cells by physically linking the t-tubule (transverse-tubule) and SR (sarcoplasmic reticulum) membranes. In humans with HCM (hypertrophic cardiomyopathy), mutations in JP2 are linked to altered Ca2+ signalling in cardiomyocytes; however, the effects of these mutations on skeletal muscle function have not been examined. In the present study, we investigated the role of the dominant-negative JP2-S165F mutation (which is associated with human HCM) in skeletal muscle. Consistent with the hypertrophy observed in human cardiac muscle, overexpression of JP2-S165F in primary mouse skeletal myotubes led to a significant increase in myotube diameter and resting cytosolic Ca2+ concentration. Single myotube Ca2+ imaging experiments showed reductions in both the excitation–contraction coupling gain and RyR (ryanodine receptor) 1-mediated Ca2+ release from the SR. Immunoprecipitation assays revealed defects in the PKC (protein kinase C)-mediated phosphorylation of the JP2-S165F mutant protein at Ser165 and in binding of JP2-S165F to the Ca2+ channel TRPC3 (transient receptor potential cation canonical-type channel 3) on the t-tubule membrane. Therefore both the hypertrophy and altered intracellular Ca2+ signalling in the JP2-S165F-expressing skeletal myotubes can be linked to altered phosphorylation of JP2 and/or altered cross-talk among Ca2+ channels on the t-tubule and SR membranes.

Oxtr/TRPV1 expression and acclimation of skeletal muscle to cold-stress in male mice

2021 ◽  
Author(s):  
Elena Conte ◽  
Adele Romano ◽  
Michela De Bellis ◽  
Maria Luisa De Ceglia ◽  
Maria Rosaria Carratù ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Cold Stress ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Male Mice ◽  
Transient Receptor ◽  
Immunohistochemical Studies ◽  
Circulating Levels

We explored the involvement of Oxytocin receptor (Oxtr)/ Transient-receptor-potential-vanilloid-1 (TRPV1) genes and Oxytocin (Oxt) on the adaptation of skeletal muscle to cold stress challenge in mice. Oxtr expression in hypothalamic paraventricular (PVN), supraoptic nuclei (SON), and hippocampus (HIPP) were evaluated by immunohistochemistry in parallel with the measurement of circulating Oxt. The Oxtr and TRPV1 gene expression in Soleus (SOL) and Tibialis Anterior (TA) muscles were investigated by RT-PCR. Histological studies of the cardiac muscle after cold stress were also performed. Male mice (n=15) were divided into controls maintained at room temperature (RT=24°C), exposed to cold stress (CS) at T=4°C for 6 hours (6h), and 5 days (5d). Immunohistochemical studies showed that Oxtr protein expression increased by 2-fold (p=0.01) in PVN and by 1.5-fold (p=0.0001) in HIPP after 6h and 5d CS, but decreased by 2-fold (p=0.026) in SON at 5d. Both Oxtr and TRPV1 gene expression increased after 6h and 5d CS in SOL and TA muscles. Oxtr vs TRPV1 gene expression in SOL and TA muscles evaluated by regression analysis was linearly correlated following CS at 6h and 5d but not at control temperature of 24+1°C, supporting the hypothesis of coupling between these genes. The circulating levels of Oxt are unaffected after 6h CS but decreased by 0.2-fold (p=0.0141) after 5d CS. This is the first report that Oxtr and TRPV1 expression are upregulated in response to cold acclimation in skeletal muscle. The up-regulation of Oxtr in PVN and HIPP balances the decrease of circulating Oxt.

scholarly journals The Contractile Phenotype of Skeletal Muscle in TRPV1 Knockout Mice Is Gender-Specific and Exercise-Dependent

Life ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 233
Author(s):  
Aude Lafoux ◽  
Sabine Lotteau ◽  
Corinne Huchet ◽  
Sylvie Ducreux
Keyword(s):  
Skeletal Muscle ◽  
Skeletal Muscles ◽  
Transient Receptor Potential ◽  
Heat Stroke ◽  
Receptor Potential ◽  
Muscle Physiology ◽  
Transient Receptor Potential Vanilloid ◽  
Noxious Heat ◽  
Contractile Phenotype ◽  
Transient Receptor

The transient receptor potential vanilloid 1 (TRPV1) belongs to the transient receptor potential superfamily of sensory receptors. TRPV1 is a non-selective cation channel permeable to Ca2+ that is capable of detecting noxious heat temperature and acidosis. In skeletal muscles, TRPV1 operates as a reticular Ca2+-leak channel and several TRPV1 mutations have been associated with two muscle disorders: malignant hyperthermia (MH) and exertional heat stroke (EHS). Although TRPV1−/− mice have been available since the 2000s, TRPV1’s role in muscle physiology has not been thoroughly studied. Therefore, the focus of this work was to characterize the contractile phenotype of skeletal muscles of TRPV1-deficient mice at rest and after four weeks of exercise. As MS and EHS have a higher incidence in men than in women, we also investigated sex-related phenotype differences. Our results indicated that, without exercise, TRPV1−/− mice improved in vivo muscle strength with an impairment of skeletal muscle in vitro twitch features, i.e., delayed contraction and relaxation. Additionally, exercise appeared detrimental to TRPV1−/− slow-twitch muscles, especially in female animals.

scholarly journals Inhibition of Polyamine Biosynthesis Reverses Ca2+ Channel Remodeling in Colon Cancer Cells

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 83 ◽  
Author(s):  
Lucía Gutiérrez ◽  
Miriam Hernández-Morales ◽  
Lucía Núñez ◽  
Carlos Villalobos
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Excitable Cells ◽  
Apoptosis Resistance ◽  
Polyamine Biosynthesis ◽  
Cancer Hallmarks ◽  
Proliferation And Apoptosis ◽  
Transient Receptor ◽  
Canonical Type ◽  
Colonic Cells

Store-operated Ca2+ entry (SOCE) is the most important Ca2+ entry pathway in non-excitable cells. Colorectal cancer (CRC) shows decreased Ca2+ store content and enhanced SOCE that correlate with cancer hallmarks and are associated to remodeling of store-operated channels (SOCs). Normal colonic cells display small, Ca2+-selective currents driven by Orai1 channels. In contrast, CRC cells display larger, non-selective currents driven by Orai1 and transient receptor potential canonical type 1 channels (TRPC1). Difluoromethylornithine (DFMO), a suicide inhibitor of ornithine decarboxylase (ODC), the limiting step in polyamine biosynthesis, strongly prevents CRC, particularly when combined with sulindac. We asked whether DFMO may reverse SOC remodeling in CRC. We found that CRC cells overexpress ODC and treatment with DFMO decreases cancer hallmarks including enhanced cell proliferation and apoptosis resistance. Consistently, DFMO enhances Ca2+ store content and decreases SOCE in CRC cells. Moreover, DFMO abolish selectively the TRPC1-dependent component of SOCs characteristic of CRC cells and this effect is reversed by the polyamine putrescine. Combination of DFMO and sulindac inhibit both SOC components and abolish SOCE in CRC cells. Finally, DFMO treatment inhibits expression of TRPC1 and stromal interaction protein 1 (STIM1) in CRC cells. These results suggest that polyamines contribute to Ca2+ channel remodeling in CRC, and DFMO may prevent CRC by reversing channel remodeling.

scholarly journals Mice Lacking Homer 1 Exhibit a Skeletal Myopathy Characterized by Abnormal Transient Receptor Potential Channel Activity

2008 ◽  
Vol 28 (8) ◽  
pp. 2637-2647 ◽  
Author(s):  
Jonathan A. Stiber ◽  
Zhu-Shan Zhang ◽  
Jarrett Burch ◽  
Jerry P. Eu ◽  
Sarah Zhang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Scaffolding Protein ◽  
Channel Activity ◽  
Skeletal Muscle Function ◽  
Cross Sectional ◽  
Transient Receptor ◽  
Duchenne's Muscular Dystrophy

ABSTRACT Transient receptor potential (TRP) channels are nonselective cation channels, several of which are expressed in striated muscle. Because the scaffolding protein Homer 1 has been implicated in TRP channel regulation, we hypothesized that Homer proteins play a significant role in skeletal muscle function. Mice lacking Homer 1 exhibited a myopathy characterized by decreased muscle fiber cross-sectional area and decreased skeletal muscle force generation. Homer 1 knockout myotubes displayed increased basal current density and spontaneous cation influx. This spontaneous cation influx in Homer 1 knockout myotubes was blocked by reexpression of Homer 1b, but not Homer 1a, and by gene silencing of TRPC1. Moreover, diminished Homer 1 expression in mouse models of Duchenne's muscular dystrophy suggests that loss of Homer 1 scaffolding of TRP channels may contribute to the increased stretch-activated channel activity observed in mdx myofibers. These findings provide direct evidence that Homer 1 functions as an important scaffold for TRP channels and regulates mechanotransduction in skeletal muscle.

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