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Proteins of the Triadic Excitation-Contraction Coupling Complex in Skeletal Muscle. 骨骼肌三联兴奋-收缩耦合复合体的蛋白质。
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-10-01 DOI: 10.1101/cshperspect.a041482
Ting Chang, Rachel Sue Zhen Yee, George G Rodney, Susan L Hamilton
{"title":"Proteins of the Triadic Excitation-Contraction Coupling Complex in Skeletal Muscle.","authors":"Ting Chang, Rachel Sue Zhen Yee, George G Rodney, Susan L Hamilton","doi":"10.1101/cshperspect.a041482","DOIUrl":"10.1101/cshperspect.a041482","url":null,"abstract":"<p><p>Excitation-contraction coupling (ECC) in skeletal muscle is mediated by mechanical coupling between the L-type voltage-dependent Ca<sup>2+</sup> channel (Ca<sub>V</sub>1.1) in the transverse tubules and the Ca<sup>2+</sup> release channel (RYR1) in the sarcoplasmic reticulum (SR). However, ECC complexes are much more complicated than just these two ion channels. Triadic Ca<sup>2+</sup> release units (CRUs) that mediate ECC in skeletal muscle are allosterically regulated complexes of ion channels, cytoplasmic modulators, SR transmembrane proteins, and lumenal Ca<sup>2+</sup> buffers. While RYR1, Ca<sub>V</sub>1.1α<sub>1s</sub>, and Ca<sub>V</sub>1.1β<sub>1a</sub>, the SH3 and cysteine-rich domain protein (STAC3) and junctophilin (JPH1 and/or JPH2) are required for voltage-gated Ca<sup>2+</sup> release, other auxiliary proteins modulate this process. In this review, we discuss what is known about the proteins in the triadic protein complex, their roles in ECC, and the mutations in the ECC proteins that give rise to skeletal muscle myopathies.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Telomeric Repeat-Containing RNA: Biogenesis, Regulation, and Functions. 端粒重复序列RNA：生物发生、调控和功能。
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-10-01 DOI: 10.1101/cshperspect.a041683
Patricia L Abreu, Valentina Riva, Luca Zardoni, Claus M Azzalin
{"title":"Telomeric Repeat-Containing RNA: Biogenesis, Regulation, and Functions.","authors":"Patricia L Abreu, Valentina Riva, Luca Zardoni, Claus M Azzalin","doi":"10.1101/cshperspect.a041683","DOIUrl":"10.1101/cshperspect.a041683","url":null,"abstract":"<p><p>Telomeric repeat-containing RNA (TERRA) molecules are transcripts comprising extended stretches of telomeric G-rich repeats, which are generated from telomeres or intrachromosomal loci. TERRA production is an evolutionarily conserved process observed across all eukaryotic kingdoms. While originally thought to localize and function only at telomeres, it is now clear that TERRA is involved in numerous cellular pathways beyond telomere maintenance, including gene expression regulation and signaling of dysfunctional telomeres to the cytoplasm and the extracellular environment. In this work, we will review key aspects of TERRA biogenesis, regulation, and functional relevance and propose models to reconcile the multiple and sometimes contradictory functions ascribed to TERRA. Based on TERRA interaction with proteins involved in disparate cellular processes, we also suggest that the full spectrum of TERRA-associated functions is still far from being completely unveiled. We anticipate that further study of this complex and fascinating RNA will reveal additional surprises in the future.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Engineered In Vitro Platforms for Mechanochemical Control of Cell Migration. 机械化学控制细胞迁移的体外工程平台。
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-10-01 DOI: 10.1101/cshperspect.a041795
Bishwa Ranjan Si, Qinling Yuan, Sanjiban Nath, Bhawana Agarwal, Alice Amitrano, Debanik Choudhury, Konstantinos Konstantopoulos
{"title":"Engineered In Vitro Platforms for Mechanochemical Control of Cell Migration.","authors":"Bishwa Ranjan Si, Qinling Yuan, Sanjiban Nath, Bhawana Agarwal, Alice Amitrano, Debanik Choudhury, Konstantinos Konstantopoulos","doi":"10.1101/cshperspect.a041795","DOIUrl":"10.1101/cshperspect.a041795","url":null,"abstract":"<p><p>Cell migration in confined environments follows distinct mechanisms compared to conventional 2D migration. By using in vitro models and incorporating extracellular cues from the tissue microenvironment, we can gain deeper insights into the complexities of cell migration. In this work, we explore various engineered in vitro models to study cell migration. We delve into biophysical tools, such as traction force microscopy, to understand how cells generate forces in response to their surroundings. We highlight the use of novel optogenetic tools for precise, spatiotemporal control of protein expression at the cellular level. Lastly, we examine emerging therapeutic strategies designed to target abnormal cell migration.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Role of Microglia in Central Nervous System Development and Plasticity. 小胶质细胞在中枢神经系统发育和可塑性中的作用
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-10-01 DOI: 10.1101/cshperspect.a041810
Dorothy P Schafer, Beth Stevens, Mariko L Bennett, Frederick C Bennett
{"title":"Role of Microglia in Central Nervous System Development and Plasticity.","authors":"Dorothy P Schafer, Beth Stevens, Mariko L Bennett, Frederick C Bennett","doi":"10.1101/cshperspect.a041810","DOIUrl":"10.1101/cshperspect.a041810","url":null,"abstract":"<p><p>The nervous system comprises a remarkably diverse and complex network of cell types, which must communicate with one another with speed, reliability, and precision. Thus, the developmental patterning and maintenance of these cell populations and their connections with one another pose a rather formidable task. Emerging data implicate microglia, the resident myeloid-derived cells of the central nervous system (CNS), in spatial patterning and synaptic wiring throughout the healthy, developing, and adult CNS. Importantly, new tools to specifically manipulate microglia function have revealed that these cellular functions translate, on a systems level, to effects on overall behavior. In this review, we give a historical perspective of work to identify microglia function in the healthy CNS, and highlight exciting new discoveries about their contributions to CNS development, maintenance, and plasticity.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Illuminating Mammalian Cell Migration in Native Tissues at Subcellular and Molecular Resolution. 在亚细胞和分子分辨率上阐明哺乳动物细胞在原生组织中的迁移。
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-09-23 DOI: 10.1101/cshperspect.a041742
Bhagawat C Subramanian, Marco Heydecker, Yeap Ng, Nicolas Melis, Roberto Weigert
{"title":"Illuminating Mammalian Cell Migration in Native Tissues at Subcellular and Molecular Resolution.","authors":"Bhagawat C Subramanian, Marco Heydecker, Yeap Ng, Nicolas Melis, Roberto Weigert","doi":"10.1101/cshperspect.a041742","DOIUrl":"https://doi.org/10.1101/cshperspect.a041742","url":null,"abstract":"<p><p>Although cell migration has been extensively investigated using in vitro model systems, the mechanisms underlying mammalian cell migration in native tissue environments remain underexplored. Moreover, efforts to directly manipulate and visualize molecular regulators in live mammalian tissues have been scarce. In this article, we first review the current insights into various single-cell migration phenomena, including stem cell types, observed in mammalian tissues under homeostatic and pathophysiological conditions. Thereafter, we discuss intravital subcellular microscopy (ISMic) as a tool to unravel membrane remodeling mechanisms underlying cell migration in live animal tissues. Lastly, we emphasize the need for innovative microscopy and complementary advanced approaches to achieve a deeper fundamental understanding of cell migration modalities and their impact on mammalian tissue in homeostasis and pathophysiology.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting Recoding by trans-Translation to Develop Antibiotics. 利用反翻译靶向重编码开发抗生素。
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-09-22 DOI: 10.1101/cshperspect.a041864
Kenneth C Keiler, Akanksha Varshney, Christine M Dunham
{"title":"Targeting Recoding by <i>trans</i>-Translation to Develop Antibiotics.","authors":"Kenneth C Keiler, Akanksha Varshney, Christine M Dunham","doi":"10.1101/cshperspect.a041864","DOIUrl":"https://doi.org/10.1101/cshperspect.a041864","url":null,"abstract":"<p><p><i>trans</i>-Translation is a recoding event in which a translating ribosome switches from the engaged messenger RNA (mRNA) to a specialized reading frame within transfer-messenger RNA (tmRNA) without releasing the nascent polypeptide, producing a protein that is encoded in two physically distinct RNA molecules. <i>trans</i>-Translation is the most abundant form of recoding and is found throughout the bacterial kingdom. In <i>Escherichia coli</i> growing in liquid culture, ∼5% of newly synthesized proteins are recoded through <i>trans</i>-translation. The importance of this pathway for pathogenic bacteria makes it a potential target for antibiotic development. This review covers the role of <i>trans</i>-translation in pathogenesis, potential points for inhibition, and the progress in developing <i>trans</i>-translation inhibitors as antibiotics.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Mechanometabolism Toolbox for Studying Cell Migration. 研究细胞迁移的机械代谢工具箱。
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-09-22 DOI: 10.1101/cshperspect.a041755
Katherine M Young, Santiago Lopez, Keefer Boone, Mehmet Acikel, Xavi Gallart, Cynthia Reinhart-King
{"title":"A Mechanometabolism Toolbox for Studying Cell Migration.","authors":"Katherine M Young, Santiago Lopez, Keefer Boone, Mehmet Acikel, Xavi Gallart, Cynthia Reinhart-King","doi":"10.1101/cshperspect.a041755","DOIUrl":"https://doi.org/10.1101/cshperspect.a041755","url":null,"abstract":"<p><p>Cell migration is greatly affected by both the physical properties of the motile cell itself and the environment through which the cell is moving. In addition to studying cellular and extracellular mechanical properties in the context of cell migration, there is a growing interest in understanding the intersection between migration, mechanics, and metabolism. In this work, we discuss the many techniques and approaches researchers are currently using to study cellular mechanics, extracellular mechanics, and metabolism in the context of cell migration. Our goal is to bring exposure to new approaches in the fields of mechanobiology and mechanometabolism and highlight the importance of studying cell migration through a mechanical lens.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Unusual Effectiveness of Evolution in Systems Neuroscience. 进化在系统神经科学中的不同寻常的有效性。
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-09-22 DOI: 10.1101/cshperspect.a041510
Arkarup Banerjee, Steven M Phelps, Justus M Kebschull
{"title":"The Unusual Effectiveness of Evolution in Systems Neuroscience.","authors":"Arkarup Banerjee, Steven M Phelps, Justus M Kebschull","doi":"10.1101/cshperspect.a041510","DOIUrl":"https://doi.org/10.1101/cshperspect.a041510","url":null,"abstract":"<p><p>This perspective advocates for \"evolutionary systems neuroscience\" as a framework combining evolutionary biology with neural circuit analysis. Evolution creates natural circuit modifications that preserve essential functions while enabling new behaviors. Modern technologies now allow researchers to investigate causal connections from genes to circuits to behaviors with unprecedented precision. By studying both convergent and divergent evolution, we can uncover both broad computational principles and specific implementation mechanisms. Across diverse examples-from insect courtship to rodent communication-we explore how targeted circuit changes drive behavioral innovation without disrupting core functions. This framework may reveal \"deep homologies\" in neural mechanisms, similar to how evolutionary developmental biology (evo-devo) identified conserved genetic toolkits in morphological development. This evolutionary lens promises not just to reveal how brains work, but why they work the way they do-providing insights that extend beyond neuroscience to complex adaptive systems more broadly.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
From Signals to Protrusions: Modeling Excitable Systems in Cell Migration. 从信号到突起：细胞迁移中可兴奋系统的建模。
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-09-22 DOI: 10.1101/cshperspect.a041746
Pablo A Iglesias, Parijat Banerjee
{"title":"From Signals to Protrusions: Modeling Excitable Systems in Cell Migration.","authors":"Pablo A Iglesias, Parijat Banerjee","doi":"10.1101/cshperspect.a041746","DOIUrl":"https://doi.org/10.1101/cshperspect.a041746","url":null,"abstract":"<p><p>Cell migration is a fundamental biological process critical for development, immune response, and wound healing, but its dysregulation contributes to pathological conditions such as cancer metastasis. Recent research has demonstrated that migration is driven by excitable signal transduction and cytoskeletal networks, which function as separate but coupled systems. The signal transduction excitable network (STEN) propagates excitatory signals, while the cytoskeletal excitable network (CEN) generates cytoskeletal protrusions. Although distinct, these networks interact dynamically: STEN regulates CEN, while CEN provides feedback to STEN, influencing cell polarization and directionality. Computational models incorporating nonlinear dynamics and reaction-diffusion systems have successfully recapitulated these interactions, shedding light on their role in pseudopod formation, chemotaxis, and mechanosensation. This review discusses recent experimental and theoretical advances, highlighting how excitable systems underlie cell motility and how mathematical modeling helps to understand their role.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chemical and Mechanical Regulation of Leukocyte Migration. 白细胞迁移的化学和机械调控。
IF 8.4 2区 生物学
Cold Spring Harbor perspectives in biology Pub Date : 2025-09-22 DOI: 10.1101/cshperspect.a041752
Jonathan H Schrope, Tanner F Robertson, Milka Sarris, Anna Huttenlocher
{"title":"Chemical and Mechanical Regulation of Leukocyte Migration.","authors":"Jonathan H Schrope, Tanner F Robertson, Milka Sarris, Anna Huttenlocher","doi":"10.1101/cshperspect.a041752","DOIUrl":"https://doi.org/10.1101/cshperspect.a041752","url":null,"abstract":"<p><p>Directed leukocyte motility is essential for immunity and host defense. Dysregulated leukocyte migration is implicated in clinical immunodeficiency and hyperinflammatory conditions. Leukocytes sense both chemical and physical cues within the environment to regulate internal migration machinery and thus coordinate the immune response and its resolution. In response to environmental cues, leukocytes cater migration strategies to both exert forces on surrounding tissues and alter the chemical environment through self-generated gradients. Here, we synthesize recent advances in our understanding of how chemical and physical cues within the tissue environment regulate leukocyte motility, with implications to develop therapeutic strategies to modulate the immune response in human disease.</p>","PeriodicalId":10494,"journal":{"name":"Cold Spring Harbor perspectives in biology","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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