Cardiac Transverse Tubules in Physiology and Heart Failure

2021 ◽  
Vol 84 (1) ◽  
Author(s):  
Katharine M. Dibb ◽  
William E. Louch ◽  
Andrew W. Trafford

In mammalian cardiac myocytes, the plasma membrane includes the surface sarcolemma but also a network of membrane invaginations called transverse (t-) tubules. These structures carry the action potential deep into the cell interior, allowing efficient triggering of Ca2+ release and initiation of contraction. Once thought to serve as rather static enablers of excitation-contraction coupling, recent work has provided a newfound appreciation of the plasticity of the t-tubule network's structure and function. Indeed, t-tubules are now understood to support dynamic regulation of the heartbeat across a range of timescales, during all stages of life, in both health and disease. This review article aims to summarize these concepts, with consideration given to emerging t-tubule regulators and their targeting in future therapies. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

2011 ◽  
Vol 278 (1719) ◽  
pp. 2714-2723 ◽  
Author(s):  
Michael Ibrahim ◽  
Julia Gorelik ◽  
Magdi H. Yacoub ◽  
Cesare M. Terracciano

The transverse tubules (t-tubules) are invaginations of the cell membrane rich in several ion channels and other proteins devoted to the critical task of excitation–contraction coupling in cardiac muscle cells (cardiomyocytes). They are thought to promote the synchronous activation of the whole depth of the cell despite the fact that the signal to contract is relayed across the external membrane. However, recent work has shown that t-tubule structure and function are complex and tightly regulated in healthy cardiomyocytes. In this review, we outline the rapidly accumulating knowledge of its novel roles and discuss the emerging evidence of t-tubule dysfunction in cardiac disease, especially heart failure. Controversy surrounds the t-tubules' regulatory elements, and we draw attention to work that is defining these elements from the genetic and the physiological levels. More generally, this field illustrates the challenges in the dissection of the complex relationship between cellular structure and function.


2022 ◽  
Vol 51 (1) ◽  
Author(s):  
Kelly R. Karch ◽  
Dalton T. Snyder ◽  
Sophie R. Harvey ◽  
Vicki H. Wysocki

Native mass spectrometry (nMS) has emerged as an important tool in studying the structure and function of macromolecules and their complexes in the gas phase. In this review, we cover recent advances in nMS and related techniques including sample preparation, instrumentation, activation methods, and data analysis software. These advances have enabled nMS-based techniques to address a variety of challenging questions in structural biology. The second half of this review highlights recent applications of these technologies and surveys the classes of complexes that can be studied with nMS. Complementarity of nMS to existing structural biology techniques and current challenges in nMS are also addressed. Expected final online publication date for the Annual Review of Biophysics, Volume 51 is May 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


Author(s):  
Marihan Hegazy ◽  
Abbey L. Perl ◽  
Sophia A. Svoboda ◽  
Kathleen J. Green

Desmosomal cadherins are a recent evolutionary innovation that make up the adhesive core of highly specialized intercellular junctions called desmosomes. Desmosomal cadherins, which are grouped into desmogleins and desmocollins, are related to the classical cadherins, but their cytoplasmic domains are tailored for anchoring intermediate filaments instead of actin to sites of cell–cell adhesion. The resulting junctions are critical for resisting mechanical stress in tissues such as the skin and heart. Desmosomal cadherins also act as signaling hubs that promote differentiation and facilitate morphogenesis, creating more complex and effective tissue barriers in vertebrate tissues. Interference with desmosomal cadherin adhesive and supra-adhesive functions leads to a variety of autoimmune, hereditary, toxin-mediated, and malignant diseases. We review our current understanding of how desmosomal cadherins contribute to human health and disease, highlight gaps in our knowledge about their regulation and function, and introduce promising new directions toward combatting desmosome-related diseases. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


2011 ◽  
Vol 21 (3) ◽  
pp. 112-117 ◽  
Author(s):  
Elizabeth Erickson-Levendoski ◽  
Mahalakshmi Sivasankar

The epithelium plays a critical role in the maintenance of laryngeal health. This is evident in that laryngeal disease may result when the integrity of the epithelium is compromised by insults such as laryngopharyngeal reflux. In this article, we will review the structure and function of the laryngeal epithelium and summarize the impact of laryngopharyngeal reflux on the epithelium. Research investigating the ramifications of reflux on the epithelium has improved our understanding of laryngeal disease associated with laryngopharyngeal reflux. It further highlights the need for continued research on the laryngeal epithelium in health and disease.


The review article discusses the possibilities of using fractal mathematical analysis to solve scientific and applied problems of modern biology and medicine. The authors show that only such an approach, related to the section of nonlinear mechanics, allows quantifying the chaotic component of the structure and function of living systems, that is a priori important additional information and expands, in particular, the possibilities of diagnostics, differential diagnosis and prediction of the course of physiological and pathological processes. A number of examples demonstrate the specific advantages of using fractal analysis for these purposes. The conclusion can be made that the expanded use of fractal analysis methods in the research work of medical and biological specialists is promising.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Fatima Amer-Sarsour ◽  
Alina Kordonsky ◽  
Yevgeny Berdichevsky ◽  
Gali Prag ◽  
Avraham Ashkenazi

AbstractUbiquitylation and deubiquitylation play a pivotal role in protein homeostasis (proteostasis). Proteostasis shapes the proteome landscape in the human brain and its impairment is linked to neurodevelopmental and neurodegenerative disorders. Here we discuss the emerging roles of deubiquitylating enzymes in neuronal function and survival. We provide an updated perspective on the genetics, physiology, structure, and function of deubiquitylases in neuronal health and disease.


2021 ◽  
Vol 72 (1) ◽  
Author(s):  
Ryan J. Emenecker ◽  
Alex S. Holehouse ◽  
Lucia C. Strader

A surge in research focused on understanding the physical principles governing the formation, properties, and function of membraneless compartments has occurred over the past decade. Compartments such as the nucleolus, stress granules, and nuclear speckles have been designated as biomolecular condensates to describe their shared property of spatially concentrating biomolecules. Although this research has historically been carried out in animal and fungal systems, recent work has begun to explore whether these same principles are relevant in plants. Effectively understanding and studying biomolecular condensates require interdisciplinary expertise that spans cell biology, biochemistry, and condensed matter physics and biophysics. As such, some involved concepts may be unfamiliar to any given individual. This review focuses on introducing concepts essential to the study of biomolecular condensates and phase separation for biologists seeking to carry out research in this area and further examines aspects of biomolecular condensates that are relevant to plant systems. Expected final online publication date for the Annual Review of Plant Biology, Volume 72 is May 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


Author(s):  
Sihan Wu ◽  
Vineet Bafna ◽  
Howard Y. Chang ◽  
Paul S. Mischel

Human genes are arranged on 23 pairs of chromosomes, but in cancer, tumor-promoting genes and regulatory elements can free themselves from chromosomes and relocate to circular, extrachromosomal pieces of DNA (ecDNA). ecDNA, because of its nonchromosomal inheritance, drives high-copy-number oncogene amplification and enables tumors to evolve their genomes rapidly. Furthermore, the circular ecDNA architecture fundamentally alters gene regulation and transcription, and the higher-order organization of ecDNA contributes to tumor pathogenesis. Consequently, patients whose cancers harbor ecDNA have significantly shorter survival. Although ecDNA was first observed more than 50 years ago, its critical importance has only recently come to light. In this review, we discuss the current state of understanding of how ecDNAs form and function as well as how they contribute to drug resistance and accelerated cancer evolution. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


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