Nicola Fameli , Cornelis van Breemen , Klaus Groschner
{"title":"纳米连接:Ca2+信号的特异性需要细胞膜内接触位点的纳米级结构","authors":"Nicola Fameli , Cornelis van Breemen , Klaus Groschner","doi":"10.1016/j.ceca.2023.102837","DOIUrl":null,"url":null,"abstract":"<div><p>Spatio-temporal definition of Ca<sup>2+</sup> signals involves the assembly of signaling complexes within the nano-architecture of contact sites between the sarco/endoplasmic reticulum (SR/ER) and the plasma membrane (PM). While the requirement of precise spatial assembly and positioning of the junctional signaling elements is well documented, the role of the nano-scale membrane architecture itself, as an ion-reflecting confinement of the signalling unit, remains as yet elusive. Utilizing the Na<sup>+</sup>/Ca<sup>2+</sup> Exchanger-1 / SR/ER Ca<sup>2+</sup> ATPase-2-mediated ER Ca<sup>2+</sup> refilling process as a junctional signalling paradigm, we provide here the first evidence for an indispensable cellular function of the junctional membrane architecture. Our stochastic modeling approach demonstrates that junctional ER Ca<sup>2+</sup> refilling operates exclusively at nano-scale membrane spacing, with a strong inverse relationship between junctional width and signaling efficiency. Our model predicts a breakdown of junctional Ca<sup>2+</sup> signaling with loss of reflecting membrane confinement. In addition we consider interactions between Ca<sup>2+</sup> and the phospholipid membrane surface, which may support interfacial Ca<sup>2+</sup> transport and promote receptor targeting. Alterations in the molecular and nano-scale membrane organization at organelle-PM contacts are suggested as a new concept in pathophysiology.</p></div>","PeriodicalId":9678,"journal":{"name":"Cell calcium","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2023-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143416023001483/pdfft?md5=cfc85bddc4ac01d6a5b5254777a31fe6&pid=1-s2.0-S0143416023001483-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Nanojunctions: Specificity of Ca2+ signaling requires nano-scale architecture of intracellular membrane contact sites\",\"authors\":\"Nicola Fameli , Cornelis van Breemen , Klaus Groschner\",\"doi\":\"10.1016/j.ceca.2023.102837\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Spatio-temporal definition of Ca<sup>2+</sup> signals involves the assembly of signaling complexes within the nano-architecture of contact sites between the sarco/endoplasmic reticulum (SR/ER) and the plasma membrane (PM). While the requirement of precise spatial assembly and positioning of the junctional signaling elements is well documented, the role of the nano-scale membrane architecture itself, as an ion-reflecting confinement of the signalling unit, remains as yet elusive. Utilizing the Na<sup>+</sup>/Ca<sup>2+</sup> Exchanger-1 / SR/ER Ca<sup>2+</sup> ATPase-2-mediated ER Ca<sup>2+</sup> refilling process as a junctional signalling paradigm, we provide here the first evidence for an indispensable cellular function of the junctional membrane architecture. Our stochastic modeling approach demonstrates that junctional ER Ca<sup>2+</sup> refilling operates exclusively at nano-scale membrane spacing, with a strong inverse relationship between junctional width and signaling efficiency. Our model predicts a breakdown of junctional Ca<sup>2+</sup> signaling with loss of reflecting membrane confinement. In addition we consider interactions between Ca<sup>2+</sup> and the phospholipid membrane surface, which may support interfacial Ca<sup>2+</sup> transport and promote receptor targeting. Alterations in the molecular and nano-scale membrane organization at organelle-PM contacts are suggested as a new concept in pathophysiology.</p></div>\",\"PeriodicalId\":9678,\"journal\":{\"name\":\"Cell calcium\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2023-11-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0143416023001483/pdfft?md5=cfc85bddc4ac01d6a5b5254777a31fe6&pid=1-s2.0-S0143416023001483-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell calcium\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0143416023001483\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell calcium","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0143416023001483","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Nanojunctions: Specificity of Ca2+ signaling requires nano-scale architecture of intracellular membrane contact sites
Spatio-temporal definition of Ca2+ signals involves the assembly of signaling complexes within the nano-architecture of contact sites between the sarco/endoplasmic reticulum (SR/ER) and the plasma membrane (PM). While the requirement of precise spatial assembly and positioning of the junctional signaling elements is well documented, the role of the nano-scale membrane architecture itself, as an ion-reflecting confinement of the signalling unit, remains as yet elusive. Utilizing the Na+/Ca2+ Exchanger-1 / SR/ER Ca2+ ATPase-2-mediated ER Ca2+ refilling process as a junctional signalling paradigm, we provide here the first evidence for an indispensable cellular function of the junctional membrane architecture. Our stochastic modeling approach demonstrates that junctional ER Ca2+ refilling operates exclusively at nano-scale membrane spacing, with a strong inverse relationship between junctional width and signaling efficiency. Our model predicts a breakdown of junctional Ca2+ signaling with loss of reflecting membrane confinement. In addition we consider interactions between Ca2+ and the phospholipid membrane surface, which may support interfacial Ca2+ transport and promote receptor targeting. Alterations in the molecular and nano-scale membrane organization at organelle-PM contacts are suggested as a new concept in pathophysiology.
期刊介绍:
Cell Calcium covers the field of calcium metabolism and signalling in living systems, from aspects including inorganic chemistry, physiology, molecular biology and pathology. Topic themes include:
Roles of calcium in regulating cellular events such as apoptosis, necrosis and organelle remodelling
Influence of calcium regulation in affecting health and disease outcomes