{"title":"β-adrenergic regulation of Ca<sup>2+</sup> signaling in heart cells.","authors":"Bo Yang, Shi-Qiang Wang, Hua-Qian Yang","doi":"10.52601/bpr.2024.240906","DOIUrl":"10.52601/bpr.2024.240906","url":null,"abstract":"<p><p>β-adrenergic receptors (βARs) play significant roles in regulating Ca<sup>2+</sup> signaling in cardiac myocytes, thus holding a key function in modulating heart performance. βARs regulate the influx of extracellular Ca<sup>2+</sup> and the release and uptake of Ca<sup>2+</sup> from the sarcoplasmic reticulum (SR) by activating key components such as L-type calcium channels (LTCCs), ryanodine receptors (RyRs) and phospholamban (PLN), mediated by the phosphorylation actions by protein kinase A (PKA). In cardiac myocytes, the presence of β<sub>2</sub>AR provides a protective mechanism against potential overstimulation of β<sub>1</sub>AR, which may aid in the restoration of cardiac dysfunctions. Understanding the Ca<sup>2+</sup> regulatory signaling pathways of βARs in cardiac myocytes and the differences among various βAR subtypes are crucial in cardiology and hold great potential for developing treatments for heart diseases.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 5","pages":"274-282"},"PeriodicalIF":0.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Min Su, Shanliang Zheng, Hao Liu, Tie-Shan Tang, Ying Hu
{"title":"Ca<sup>2+</sup> homeostasis: a potential target for cancer therapies.","authors":"Min Su, Shanliang Zheng, Hao Liu, Tie-Shan Tang, Ying Hu","doi":"10.52601/bpr.2024.230023","DOIUrl":"10.52601/bpr.2024.230023","url":null,"abstract":"<p><p>Calcium ions (Ca<sup>2+</sup>) play a crucial role as secondary messengers in both excitable and non-excitable cells. A complex system of proteins and molecules involved in calcium handling allows Ca<sup>2+</sup> signals to be transduced. In cancer cells, mutations, aberrant expression, and dysregulation of these calcium handling toolkit proteins disrupt the normal Ca<sup>2+</sup> flux between extracellular space, cytosol, endoplasmic reticulum and mitochondria, as well as the spatio-temporal patterns of Ca<sup>2+</sup> signalling. This leads to the dysregulation of calcium-dependent effectors that control key signaling pathways involved in cancer cell proliferation, survival and invasion. Although there has been progressing in understanding the remodelling of calcium homeostasis in cancer cells and identifying key calcium transport molecules that promote malignant phenotypes, much work remains to be done to translate these fundamental findings into new tools for diagnosing and treating cancer by targeting Ca<sup>2+</sup> homeostasis.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 5","pages":"283-292"},"PeriodicalIF":0.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Oligomeric rearrangement may regulate channel activity.","authors":"Yue Ren, Xue Yang, Yuequan Shen","doi":"10.52601/bpr.2023.230018","DOIUrl":"10.52601/bpr.2023.230018","url":null,"abstract":"<p><p>Channels are typically gated by several factors, including voltage, ligand and mechanical force. Most members of the calcium homeostasis modulator (CALHM) protein family, large-pore ATP release channels, exist in different oligomeric states. Dynamic conversions between CALHM1 heptamers and octamers to gate the channel were proposed. Meanwhile, the latest study observed that the transient receptor potential vanilloid 3 (TRPV3) channel adopts a dynamic transition between pentamers and canonical tetramers in response to small molecule treatment. These results suggest that oligomeric rearrangement may add a new layer to regulate the channel activities.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 5","pages":"293-296"},"PeriodicalIF":0.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The rectification of heterotypic Cx46/Cx50 gap junction channels depends on intracellular magnesium.","authors":"Honghong Chen, Donglin Bai","doi":"10.52601/bpr.2024.240015","DOIUrl":"10.52601/bpr.2024.240015","url":null,"abstract":"<p><p>Gap junction (GJ) intercellular communication is crucial in many physiological and pathological processes. A GJ channel is formed by head-to-head docking of two hexameric hemichannels from two neighboring cells. Heterotypic GJ channels formed by two different homomeric connexin hemichannels often display rectification properties in the current-voltage relationship while the underlying mechanisms are not fully clear. Here we studied heterotypic Cx46/Cx50 GJs at a single GJ channel level. Our data showed unitary Cx46/Cx50 GJ channel conductance (γ<sub>j</sub>) rectification when 5 mmol/L Mg<sup>2+</sup> was included in the patch pipette solution, while no γ<sub>j</sub> rectification was observed when no Mg<sup>2+</sup> was added. Including 5 mmol/L Mg<sup>2+</sup> in pipette solution significantly decreased the γ<sub>j</sub> of homotypic Cx46 GJ with little change in homotypic Cx50 γ<sub>j</sub>. A missense point variant in Cx46 (E43F) reduced the Mg<sup>2+</sup>-dependent reduction in γ<sub>j</sub> of Cx46 E43F GJ, indicating that E43 might be partially responsible for Mg<sup>2+</sup>-dependent decrease in γ<sub>j</sub> of Cx46. A comprehensive understanding of Mg<sup>2+</sup> modulation of GJ at the individual channel level is useful in understanding factors in modulating GJ-mediated intercellular communication in health and diseases.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 5","pages":"336-348"},"PeriodicalIF":0.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Golgi Ca<sup>2+</sup> stores, and original contributions by Prof. Shao Bai Xue.","authors":"Zong Jie Cui","doi":"10.52601/bpr.2023.230015","DOIUrl":"10.52601/bpr.2023.230015","url":null,"abstract":"<p><p>The Golgi apparatus serves as a distinct part of intracellular Ca<sup>2+</sup> stores. Here, the early discovery by Professor Shao Bai Xue is reviewed, and the recent progress in the field is outlined. Golgi Ca<sup>2+</sup> stores-related functional proteins, such as secretory pathway Ca<sup>2+</sup> ATPases (SPCA1/2) and the Golgi-specific Ca<sup>2+</sup> releasing channel Golgi anti-apoptotic protein (GAAP), as well as the recently defined Golgi-specific Ca<sup>2+</sup> release agent emetine, collectively corroborate the concept of the Golgi apparatus as unique internal Ca<sup>2+</sup> stores.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 5","pages":"266-273"},"PeriodicalIF":0.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fan Xu, Jing-Jing Li, Eric Yang, Yi Zhang, Wenjun Xie
{"title":"Assaying sarcoplasmic reticulum Ca<sup>2+</sup>-leak in mouse atrial myocytes.","authors":"Fan Xu, Jing-Jing Li, Eric Yang, Yi Zhang, Wenjun Xie","doi":"10.52601/bpr.2023.230044","DOIUrl":"10.52601/bpr.2023.230044","url":null,"abstract":"<p><p>More and more studies have suggested an essential role of sarcoplasmic reticulum (SR) Ca<sup>2+</sup> leak of atrial myocytes in atrial diseases such as atrial fibrillation (AF). The increasing interest in atrial Ca<sup>2+</sup> signaling makes it necessary to develop a more accurate approach for Ca<sup>2+</sup> measurement in atrial myocytes due to obvious differences between atrial and ventricular Ca<sup>2+</sup> handling. In the present study, we proposed a new approach for quantifying total SR Ca<sup>2+</sup> leak in atrial myocytes with confocal line-scan Ca<sup>2+</sup> images. With a very precious approximation of the histogram of normalized line-scan Ca<sup>2+</sup> images by using a modified Gaussian distribution, we separated the signal pixel components from noisy pixels and extracted two new dimensionless parameters, <i>F</i> <sub>signals</sub> and <i>R</i> <sub>signals</sub>, to reflect the summation of signal pixels and their release components, respectively. In the presence of tetracaine blocking SR Ca<sup>2+</sup> leak, the two parameters were very close to 0, and in atrial myocytes under normal conditions, the two parameters are well positive correlative with Ca<sup>2+</sup> spark frequency and total signal mass, the two classic readouts for SR Ca<sup>2+</sup> leak. Consistent with Ca<sup>2+</sup> Spark readouts, the two parameters quantified a significant increase of SR Ca<sup>2+</sup> leak in atrial myocytes from mice harboring a leaky type 2 ryanodine receptor mutation (RyR2-R2474S<sup>+/-</sup>) compared to the WT group. Collectively, this study proposed a simple and effective approach to quantify SR Ca<sup>2+</sup> leak in atrial myocytes, which may benefit research on calcium signaling in atrial physiology and diseases.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 5","pages":"297-303"},"PeriodicalIF":0.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yutong Su, Yongshen Liang, Menghao Xu, Beibei Gao, Siyuan Zhang, Eric Yang, Shuai Yin, Da Li, Zhangqin Huang, Wenjun Xie
{"title":"Modeling sarcoplasmic reticulum Ca<sup>2+</sup> in rat cardiomyocytes.","authors":"Yutong Su, Yongshen Liang, Menghao Xu, Beibei Gao, Siyuan Zhang, Eric Yang, Shuai Yin, Da Li, Zhangqin Huang, Wenjun Xie","doi":"10.52601/bpr.2024.240012","DOIUrl":"10.52601/bpr.2024.240012","url":null,"abstract":"<p><p>The sarcoplasmic reticulum (SR) primarily serves as the intracellular Ca<sup>2+</sup> store in cardiac myocytes, mediating cellular function under cardiac physiology and diseases. However, the properties of cardiac SR Ca<sup>2+</sup> have not yet been fully determined, particularly in rats and mice, which are the most commonly used experimental species in studies on cardiac physiology and diseases. Here, we developed a spatially detailed numerical model to deduce Ca<sup>2+</sup> movements inside the junctional SR (jSR) cisternae of rat cardiomyocytes. Our model accurately reproduced the jSR Ca<sup>2+</sup> kinetics of local and global SR Ca<sup>2+</sup> releases reported in a recent experimental study. With this model, we revealed that jSR Ca<sup>2+</sup> kinetics was mostly determined by the total release flux via type 2 ryanodine receptor (RyR2) channels but not by RyR2 positioning. Although Ca<sup>2+</sup> diffusion in global SR was previously reported to be slow, our simulation demonstrated that Ca<sup>2+</sup> diffused very quickly inside local jSR cisternae and the decrease in the diffusion coefficient resulted in a significant reduction of jSR Ca<sup>2+</sup> depletion amplitude. Intracellular Ca<sup>2+</sup> was typically experimentally detected with fluorescence dye. Our simulation revealed that when the dynamical characteristics of fluorescence dye exerted a minimal effect on actual Ca<sup>2+</sup> mobility inside jSR, the reaction rate of the dye with Ca<sup>2+</sup> could significantly affect apparent jSR Ca<sup>2+</sup> kinetics. Therefore, loading a chemical fluorescence dye with fast kinetics, such as Fluo-5N, into SR is important for Ca<sup>2+</sup> measurement inside SR. Overall, our model provides new insights into deciphering Ca<sup>2+</sup> handling inside nanoscopic jSR cisternae in rat cardiomyocytes.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 5","pages":"328-335"},"PeriodicalIF":0.0,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Single-cell transcriptomics reveals neural stem cell trans-differentiation and cell subpopulations in whole heart decellularized extracellular matrix.","authors":"Xiaoning Yang, Yuwei Zhao, Wei Liu, Zhongbao Gao, Chunlan Wang, Changyong Wang, Siwei Li, Xiao Zhang","doi":"10.52601/bpr.2024.240011","DOIUrl":"https://doi.org/10.52601/bpr.2024.240011","url":null,"abstract":"<p><p>The whole heart decellularized extracellular matrix (ECM) has become a promising scaffold material for cardiac tissue engineering. Our previous research has shown that the whole heart acellular matrix possesses the memory function regulating neural stem cells (NSCs) trans-differentiating to cardiac lineage cells. However, the cell subpopulations and phenotypes in the trans-differentiation of NSCs have not been clearly identified. Here, we performed single-cell RNA sequencing and identified 2,765 cells in the recellularized heart with NSCs revealing the cellular diversity of cardiac and neural lineage, confirming NSCs were capable of trans-differentiating into the cardiac lineage while maintaining the original ability to differentiate into the neural lineage. Notably, the trans-differentiated heart-like cells have dual signatures of neuroectoderm and cardiac mesoderm. This study unveils an in-depth mechanism underlying the trans-differentiation of NSCs and provides a new opportunity and theoretical basis for cardiac regeneration.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 4","pages":"241-253"},"PeriodicalIF":0.0,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11399890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Met1-linked ubiquitination in cell signaling regulation.","authors":"Yanmin Guo, Yuqin Zhao, Yu-Sheng Cong","doi":"10.52601/bpr.2024.230030","DOIUrl":"https://doi.org/10.52601/bpr.2024.230030","url":null,"abstract":"<p><p>Met1-linked ubiquitination (Met1-Ub), also known as linear ubiquitination, is a newly identified atypical type of polyubiquitination that is assembled via the N-terminal methionine (Met1) rather than an internal lysine (Lys) residue of ubiquitin. The linear ubiquitin chain assembly complex (LUBAC) composed of HOIP, HOIL-1L and SHARPIN is the sole E3 ubiquitin ligase that specifically generates Met1-linked ubiquitin chains. The physiological role of LUBAC-mediated Met1-Ub has been first described as activating NF-κB signaling through the Met1-Ub modification of NEMO. However, accumulating evidence shows that Met1-Ub is broadly involved in other cellular pathways including MAPK, Wnt/β-Catenin, PI3K/AKT and interferon signaling, and participates in various cellular processes including angiogenesis, protein quality control and autophagy, suggesting that Met1-Ub harbors a potent signaling capacity. Here, we review the formation and cellular functions of Met1-linked ubiquitin chains, with an emphasis on the recent advances in the cellular mechanisms by which Met1-Ub controls signaling transduction.</p>","PeriodicalId":93906,"journal":{"name":"Biophysics reports","volume":"10 4","pages":"230-240"},"PeriodicalIF":0.0,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11399889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}