-
International Journal of Molecular... Nov 2020The regulation of gene expression is a fundamental process enabling cells to respond to internal and external stimuli or to execute developmental programs. Changes in... (Review)
Review
The regulation of gene expression is a fundamental process enabling cells to respond to internal and external stimuli or to execute developmental programs. Changes in gene expression are highly dynamic and depend on many intrinsic and extrinsic factors. In this review, we highlight the dynamic nature of transient gene expression changes to better understand cell physiology and development in general. We will start by comparing recent in vivo procedures to capture gene expression in real time. Intrinsic factors modulating gene expression dynamics will then be discussed, focusing on chromatin modifications. Furthermore, we will dissect how cell physiology or age impacts on dynamic gene regulation and especially discuss molecular insights into acquired transcriptional memory. Finally, this review will give an update on the mechanisms of heterogeneous gene expression among genetically identical individual cells. We will mainly focus on state-of-the-art developments in the yeast model but also cover higher eukaryotic systems.
Topics: Animals; Cell Physiological Phenomena; Gene Expression; Gene Expression Regulation, Developmental; Genetic Heterogeneity; Humans; Molecular Biology; Molecular Imaging; Single-Cell Analysis; Transcription, Genetic
PubMed: 33167354
DOI: 10.3390/ijms21218278 -
Journal of the Royal Society, Interface May 2020The last five decades of molecular and systems biology research have provided unprecedented insights into the molecular and genetic basis of many cellular processes....
The last five decades of molecular and systems biology research have provided unprecedented insights into the molecular and genetic basis of many cellular processes. Despite these insights, however, it is arguable that there is still only limited predictive understanding of cell behaviours. In particular, the basis of heterogeneity in single-cell behaviour and the initiation of many different metabolic, transcriptional or mechanical responses to environmental stimuli remain largely unexplained. To go beyond the , the understanding of cell behaviours emerging from molecular genetics must be complemented with physical and physiological ones, focusing on the intracellular and extracellular conditions within and around cells. Here, we argue that such a combination of genetics, physics and physiology can be grounded on a bioelectrical conceptualization of cells. We motivate the reasoning behind such a proposal and describe examples where a bioelectrical view has been shown to, or can, provide predictive biological understanding. In addition, we discuss how this view opens up novel ways to control cell behaviours by electrical and electrochemical means, setting the stage for the emergence of bioelectrical engineering.
Topics: Cell Physiological Phenomena; Physics
PubMed: 32429828
DOI: 10.1098/rsif.2020.0013 -
American Journal of Physiology. Cell... Jul 2004Cells face not only a complex biochemical environment but also a diverse biomechanical environment. How cells respond to variations in mechanical forces is critical in... (Review)
Review
Cells face not only a complex biochemical environment but also a diverse biomechanical environment. How cells respond to variations in mechanical forces is critical in homeostasis and many diseases. The mechanisms by which mechanical forces lead to eventual biochemical and molecular responses remain undefined, and unraveling this mystery will undoubtedly provide new insight into strengthening bone, growing cartilage, improving cardiac contractility, and constructing tissues for artificial organs. In this article we review the physical bases underlying the mechanotransduction process, techniques used to apply controlled mechanical stresses on living cells and tissues to probe mechanotransduction, and some of the important lessons that we are learning from mechanical stimulation of cells with precisely controlled forces.
Topics: Cell Physiological Phenomena; Humans; Mechanotransduction, Cellular; Physical Stimulation; Signal Transduction
PubMed: 15189819
DOI: 10.1152/ajpcell.00559.2003 -
Trends in Pharmacological Sciences Feb 2016The study of mechanobiology is now widespread. The impact of cell and tissue mechanics on cellular responses is well appreciated. However, knowledge of the impact of... (Review)
Review
The study of mechanobiology is now widespread. The impact of cell and tissue mechanics on cellular responses is well appreciated. However, knowledge of the impact of cell and tissue mechanics on pharmacological responsiveness, and its application to drug screening and mechanistic investigations, have been very limited in scope. We emphasize the need for a heightened awareness of the important bidirectional influence of drugs and biomechanics in all living systems. We propose that the term 'mechanopharmacology' be applied to approaches that employ in vitro systems, biomechanically appropriate to the relevant (patho)physiology, to identify new drugs and drug targets. This article describes the models and techniques that are being developed to transform drug screening and evaluation, ranging from a 2D environment to the dynamic 3D environment of the target expressed in the disease of interest.
Topics: Biomechanical Phenomena; Cell Physiological Phenomena; Compressive Strength; Drug Evaluation, Preclinical; Humans; Pharmacology; Shear Strength; Tensile Strength
PubMed: 26651416
DOI: 10.1016/j.tips.2015.10.005 -
Cell Calcium Sep 2018Ca flux across the inner mitochondrial membrane (IMM) regulates cellular bioenergetics, intra-cellular cytoplasmic Ca signals, and various cell death pathways. Ca entry... (Review)
Review
Ca flux across the inner mitochondrial membrane (IMM) regulates cellular bioenergetics, intra-cellular cytoplasmic Ca signals, and various cell death pathways. Ca entry into the mitochondria occurs due to the highly negative membrane potential (ΔΨ) through a selective inward rectifying MCU channel. In addition to being regulated by various mitochondrial matrix resident proteins such as MICUs, MCUb, MCUR1 and EMRE, the channel is transcriptionally regulated by upstream Ca cascade, post transnational modification and by divalent cations. The mode of regulation either inhibits or enhances MCU channel activity and thus regulates mitochondrial metabolism and cell fate.
Topics: Animals; Calcium; Calcium Channels; Cell Death; Cell Physiological Phenomena; Cytosol; Humans; Membrane Potential, Mitochondrial; Mitochondria; Mitochondrial Membrane Transport Proteins; Mitochondrial Membranes
PubMed: 29980025
DOI: 10.1016/j.ceca.2018.06.006 -
Seminars in Fetal & Neonatal Medicine Dec 2012The importance of the involvement of non-protein coding RNAs in biological processes has become evident in recent years along with the identification of the... (Review)
Review
The importance of the involvement of non-protein coding RNAs in biological processes has become evident in recent years along with the identification of the transcriptional regulatory mechanisms that allow them to exert their roles. MicroRNAs (miRNAs) are a novel class of small non-coding RNA that regulates messenger RNA abundance. The capacity of each miRNA to target several transcripts suggests an ability to build a complex regulatory network for fine tuning gene expression; a mechanism by which they are thought to regulate cell fate, proliferation and identity. The brain expresses more distinct miRNAs than any other tissue in vertebrates and it presents an impressive variety of cell types, including many different classes of neurons. Here we review more than 10 years of miRNA research, and discuss the most important findings that have established miRNAs as key regulators of neuronal development.
Topics: Brain; Cell Physiological Phenomena; Gene Expression Regulation; Gene Regulatory Networks; Genetic Code; Genetic Research; Humans; MicroRNAs; Neurogenesis; Protein Biosynthesis; RNA, Small Untranslated
PubMed: 22906916
DOI: 10.1016/j.siny.2012.07.008 -
Molecular Cell Feb 2013Metabolism impacts all cellular functions and plays a fundamental role in biology. In the last century, our knowledge of metabolic pathway architecture and the genomic... (Review)
Review
Metabolism impacts all cellular functions and plays a fundamental role in biology. In the last century, our knowledge of metabolic pathway architecture and the genomic landscape of disease has increased exponentially. Combined with these insights, advances in analytical methods for quantifying metabolites and systems approaches to analyze these data now provide powerful tools to study metabolic regulation. Here we review the diverse mechanisms cells use to adapt metabolism to specific physiological states and discuss how metabolic flux analyses can be applied to identify important regulatory nodes to understand normal and pathological cell physiology.
Topics: Animals; Cell Physiological Phenomena; Cells; Glycolysis; Humans; Metabolic Networks and Pathways; Models, Biological
PubMed: 23395269
DOI: 10.1016/j.molcel.2013.01.018 -
Physiological Reviews Oct 2017Junctional adhesion molecules (JAM)-A, -B and -C are cell-cell adhesion molecules of the immunoglobulin superfamily which are expressed by a variety of tissues, both... (Review)
Review
Junctional adhesion molecules (JAM)-A, -B and -C are cell-cell adhesion molecules of the immunoglobulin superfamily which are expressed by a variety of tissues, both during development and in the adult organism. Through their extracellular domains, they interact with other adhesion receptors on opposing cells. Through their cytoplasmic domains, they interact with PDZ domain-containing scaffolding and signaling proteins. In combination, these two properties regulate the assembly of signaling complexes at specific sites of cell-cell adhesion. The multitude of molecular interactions has enabled JAMs to adopt distinct cellular functions such as the regulation of cell-cell contact formation, cell migration, or mitotic spindle orientation. Not surprisingly, JAMs regulate diverse processes such as epithelial and endothelial barrier formation, hemostasis, angiogenesis, hematopoiesis, germ cell development, and the development of the central and peripheral nervous system. This review summarizes the recent progress in the understanding of JAMs, including their characteristic structural features, their molecular interactions, their cellular functions, and their contribution to a multitude of processes during vertebrate development and homeostasis.
Topics: Animals; Cell Adhesion; Cell Physiological Phenomena; Gene Expression Regulation; Immunoglobulins; Junctional Adhesion Molecules
PubMed: 28931565
DOI: 10.1152/physrev.00004.2017 -
Biochimica Et Biophysica Acta Apr 2011Growth factor-stimulated or cancerous cells require sufficient nutrients to meet the metabolic demands of cell growth and division. If nutrients are insufficient,... (Review)
Review
Growth factor-stimulated or cancerous cells require sufficient nutrients to meet the metabolic demands of cell growth and division. If nutrients are insufficient, metabolic checkpoints are triggered that lead to cell cycle arrest and the activation of the intrinsic apoptotic cascade through a process dependent on the Bcl-2 family of proteins. Given the connections between metabolism and apoptosis, the notion of targeting metabolism to induce cell death in cancer cells has recently garnered much attention. However, the signaling pathways by which metabolic stresses induce apoptosis have not as of yet been fully elucidated. Thus, the best approach to this promising therapeutic avenue remains unclear. This review will discuss the intricate links between metabolism, growth, and intrinsic apoptosis and will consider ways in which manipulation of metabolism might be exploited to promote apoptotic cell death in cancer cells. This article is part of a Special Issue entitled Mitochondria: the deadly organelle.
Topics: Animals; Apoptosis; Cell Physiological Phenomena; Cell Proliferation; Humans
PubMed: 20816705
DOI: 10.1016/j.bbamcr.2010.08.011 -
American Journal of Physiology. Cell... Dec 2013In Metazoa, a polarized epithelium forms a single-cell-layered barrier that separates the outside from the inside of the organism. In tubular epithelia, the apical side... (Review)
Review
In Metazoa, a polarized epithelium forms a single-cell-layered barrier that separates the outside from the inside of the organism. In tubular epithelia, the apical side of the cell is constricted relative to the basal side, forming a wedge-shaped cell that can pack into a tube. Apical constriction is mediated by actomyosin activity. In higher animals, apical actomyosin is connected between cells by specialized cell-cell junctions that contain a classical cadherin, the Wnt signaling protein β-catenin, and the actin-binding protein α-catenin. The molecular mechanisms that lead to selective accumulation of myosin at the apical surface of cells are poorly understood. We found that the nonmetazoan Dictyostelium discoideum forms a polarized epithelium that surrounds the stalk tube at the tip of the multicellular fruiting body. Although D. discoideum lacks a cadherin homolog, it expresses homologs of β- and α-catenin. Both catenins are essential for formation of the tip epithelium, polarized protein secretion, and proper multicellular morphogenesis. Myosin localizes apically in tip epithelial cells, and it appears that constriction of this epithelial tube is required for proper morphogenesis. Localization of myosin II is controlled by the protein IQGAP1 and its binding partners cortexillins I and II, which function downstream of α- and β-catenin to exclude myosin from the basolateral cortex and promote apical accumulation of myosin. These studies show that the function of catenins in cell polarity predates the evolution of Wnt signaling and classical cadherins, and that apical localization of myosin is a morphogenetic mechanism conserved from nonmetazoans to vertebrates.
Topics: Animals; Cell Physiological Phenomena; Cell Polarity; Dictyostelium; Epithelial Cells; Evolution, Molecular; Humans
PubMed: 24067914
DOI: 10.1152/ajpcell.00233.2013