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Cell Feb 2018The extracellular space (ECS) of the brain has an extremely complex spatial organization, which has defied conventional light microscopy. Consequently, despite a marked...
The extracellular space (ECS) of the brain has an extremely complex spatial organization, which has defied conventional light microscopy. Consequently, despite a marked interest in the physiological roles of brain ECS, its structure and dynamics remain largely inaccessible for experimenters. We combined 3D-STED microscopy and fluorescent labeling of the extracellular fluid to develop super-resolution shadow imaging (SUSHI) of brain ECS in living organotypic brain slices. SUSHI enables quantitative analysis of ECS structure and reveals dynamics on multiple scales in response to a variety of physiological stimuli. Because SUSHI produces sharp negative images of all cellular structures, it also enables unbiased imaging of unlabeled brain cells with respect to their anatomical context. Moreover, the extracellular labeling strategy greatly alleviates problems of photobleaching and phototoxicity associated with traditional imaging approaches. As a straightforward variant of STED microscopy, SUSHI provides unprecedented access to the structure and dynamics of live brain ECS and neuropil.
Topics: Animals; Brain; Cell Movement; Coloring Agents; Electrophysiological Phenomena; Epilepsy; Extracellular Space; Female; Glutamates; Imaging, Three-Dimensional; Male; Mice, Inbred C57BL; Neurons; Neuropil; Osmosis; Synapses
PubMed: 29474910
DOI: 10.1016/j.cell.2018.02.007 -
Anatomical Record (Hoboken, N.J. : 2007) Dec 2018Microridges are highly distinctive "fingerprint"-patterned structures situated on the outer surface of superficial layer cells of the epithelium. An F-actin-based... (Review)
Review
Microridges are highly distinctive "fingerprint"-patterned structures situated on the outer surface of superficial layer cells of the epithelium. An F-actin-based cytoskeleton is the underlying core structural component of microridges. The basis for much of what is known about microridges has been provided by in vivo and in vitro fish epithelial systems. Nonetheless the microridge literature is quite small, especially when compared with other actin-based cellular structures such as those involved in cell motility. A PubMed search of the terms "Microridges" yields 261 citations from the mid-1970s to the writing of this review. "Microplicae," an alternative name for microridges, and "Actin Microridges" search terms give 204 and 8 references, respectively, in the same time period. By comparison a search of "Lamellipodia" over the same time period yields over 6,400 citations for this important motility structure while a search of the associated "filopodia" results in close to 7,300 articles. Despite the near-ubiquity of microridges in epithelia across species the study of these structures has clearly been neglected. In-depth analysis of microridge molecular composition is very limited while their function remains unclear. This review draws upon information derived from studies of fish as well as mammalian species to provide a more comprehensive view of these structures. The wide-spread distribution of these structures between species and various tissues indicate the microridges have important and common functions in healthy organisms. Conversely, disease conditions may show alterations in microridge structure and function and thus warrant further investigation. Anat Rec, 301:2037-2050, 2018. © 2018 Wiley Periodicals, Inc.
Topics: Actin Cytoskeleton; Actins; Animals; Epithelium; Humans
PubMed: 30414250
DOI: 10.1002/ar.23965 -
Molecular Cell Oct 2010Organisms must survive a variety of stressful conditions, including sudden temperature increases that damage important cellular structures and interfere with essential... (Review)
Review
Organisms must survive a variety of stressful conditions, including sudden temperature increases that damage important cellular structures and interfere with essential functions. In response to heat stress, cells activate an ancient signaling pathway leading to the transient expression of heat shock or heat stress proteins (Hsps). Hsps exhibit sophisticated protection mechanisms, and the most conserved Hsps are molecular chaperones that prevent the formation of nonspecific protein aggregates and assist proteins in the acquisition of their native structures. In this Review, we summarize the concepts of the protective Hsp network.
Topics: Animals; Cytoskeleton; Eukaryotic Cells; Heat-Shock Proteins; Heat-Shock Response; Humans; Models, Biological; Organelles; Signal Transduction
PubMed: 20965420
DOI: 10.1016/j.molcel.2010.10.006 -
Biomolecular Concepts Feb 2016The multifaceted protein clusterin (CLU) has been challenging researchers for more than 35 years. The characterization of CLU as a molecular chaperone was one of the... (Review)
Review
The multifaceted protein clusterin (CLU) has been challenging researchers for more than 35 years. The characterization of CLU as a molecular chaperone was one of the major breakthroughs in CLU research. Today, secretory clusterin (sCLU), also known as apolipoprotein J (apoJ), is considered one of the most important extracellular chaperones ever found. It is involved in a broad range of physiological and pathophysiological functions, where it exerts a cytoprotective role. Descriptions of various forms of intracellular CLU have led to further and even contradictory functions. To untangle the current state of knowledge of CLU, this review will combine old views in the field, with new discoveries to highlight the nature and function of this fascinating protein(s). In this review, we further describe the expression and subcellular location of various CLU forms. Moreover, we discuss recent insights into the structure of CLU and assess how structural properties as well as the redox environment determine the chaperone activity of CLU. Eventually, the review connects the biochemistry and molecular cell biology of CLU with medical aspects, to formulate a hypothesis of a CLU function in health and disease.
Topics: Animals; Cellular Structures; Clusterin; Humans; Oxidative Stress; Protein Conformation
PubMed: 26673020
DOI: 10.1515/bmc-2015-0026 -
Comprehensive Physiology Apr 2011The nucleus is the distinguishing feature of eukaryotic cells. Until recently, it was often considered simply as a unique compartment containing the genetic information... (Review)
Review
The nucleus is the distinguishing feature of eukaryotic cells. Until recently, it was often considered simply as a unique compartment containing the genetic information of the cell and associated machinery, without much attention to its structure and mechanical properties. This article provides compelling examples that illustrate how specific nuclear structures are associated with important cellular functions, and how defects in nuclear mechanics can cause a multitude of human diseases. During differentiation, embryonic stem cells modify their nuclear envelope composition and chromatin structure, resulting in stiffer nuclei that reflect decreased transcriptional plasticity. In contrast, neutrophils have evolved characteristic lobulated nuclei that increase their physical plasticity, enabling passage through narrow tissue spaces in their response to inflammation. Research on diverse cell types further demonstrates how induced nuclear deformations during cellular compression or stretch can modulate cellular function. Pathological examples of disturbed nuclear mechanics include the many diseases caused by mutations in the nuclear envelope proteins lamin A/C and associated proteins, as well as cancer cells that are often characterized by abnormal nuclear morphology. In this article, we will focus on determining the functional relationship between nuclear mechanics and cellular (dys-)function, describing the molecular changes associated with physiological and pathological examples, the resulting defects in nuclear mechanics, and the effects on cellular function. New insights into the close relationship between nuclear mechanics and cellular organization and function will yield a better understanding of normal biology and will offer new clues into therapeutic approaches to the various diseases associated with defective nuclear mechanics.
Topics: Animals; Cell Differentiation; Cell Nucleus; Humans; Neoplasms
PubMed: 23737203
DOI: 10.1002/cphy.c100038 -
Angewandte Chemie (International Ed. in... 2009The study of biomolecules in their native environments is a challenging task because of the vast complexity of cellular systems. Technologies developed in the last few...
The study of biomolecules in their native environments is a challenging task because of the vast complexity of cellular systems. Technologies developed in the last few years for the selective modification of biological species in living systems have yielded new insights into cellular processes. Key to these new techniques are bioorthogonal chemical reactions, whose components must react rapidly and selectively with each other under physiological conditions in the presence of the plethora of functionality necessary to sustain life. Herein we describe the bioorthogonal chemical reactions developed to date and how they can be used to study biomolecules.
Topics: Alkynes; Animals; Azides; Biochemical Phenomena; Biochemistry; Cellular Structures; Fluorescent Dyes; Green Fluorescent Proteins; Humans; Indicators and Reagents; Molecular Sequence Data; Molecular Structure; Staining and Labeling
PubMed: 19714693
DOI: 10.1002/anie.200900942 -
Cold Spring Harbor Perspectives in... Aug 2015Organelle function is often directly related to organelle size. However, it is not necessarily absolute size but the organelle-to-cell-size ratio that is critical.... (Review)
Review
Organelle function is often directly related to organelle size. However, it is not necessarily absolute size but the organelle-to-cell-size ratio that is critical. Larger cells generally have increased metabolic demands, must segregate DNA over larger distances, and require larger cytokinetic rings to divide. Thus, organelles often must scale to the size of the cell. The need for scaling is particularly acute during early development during which cell size can change rapidly. Here, we highlight scaling mechanisms for cellular structures as diverse as centrosomes, nuclei, and the mitotic spindle, and distinguish them from more general mechanisms of size control. In some cases, scaling is a consequence of the underlying mechanism of organelle size control. In others, size-control mechanisms are not obviously related to cell size, implying that scaling results indirectly from cell-size-dependent regulation of size-control mechanisms.
Topics: Animals; Cell Nucleus; Cell Size; Centrosome; Energy Metabolism; Models, Biological; Organelle Size; Spindle Apparatus; Xenopus
PubMed: 26254310
DOI: 10.1101/cshperspect.a019067 -
Biology Open Sep 2021Well-orchestrated intercellular communication networks are pivotal to maintaining cardiac homeostasis and to ensuring adaptative responses and repair after injury.... (Review)
Review
Well-orchestrated intercellular communication networks are pivotal to maintaining cardiac homeostasis and to ensuring adaptative responses and repair after injury. Intracardiac communication is sustained by cell-cell crosstalk, directly via gap junctions (GJ) and tunneling nanotubes (TNT), indirectly through the exchange of soluble factors and extracellular vesicles (EV), and by cell-extracellular matrix (ECM) interactions. GJ-mediated communication between cardiomyocytes and with other cardiac cell types enables electrical impulse propagation, required to sustain synchronized heart beating. In addition, TNT-mediated organelle transfer has been associated with cardioprotection, whilst communication via EV plays diverse pathophysiological roles, being implicated in angiogenesis, inflammation and fibrosis. Connecting various cell populations, the ECM plays important functions not only in maintaining the heart structure, but also acting as a signal transducer for intercellular crosstalk. Although with distinct etiologies and clinical manifestations, intercellular communication derailment has been implicated in several cardiac disorders, including myocardial infarction and hypertrophy, highlighting the importance of a comprehensive and integrated view of complex cell communication networks. In this review, I intend to provide a critical perspective about the main mechanisms contributing to regulate cellular crosstalk in the heart, which may be considered in the development of future therapeutic strategies, using cell-based therapies as a paradigmatic example. This Review has an associated Future Leader to Watch interview with the author.
Topics: Cell Communication; Cell Membrane Structures; Extracellular Matrix; Gap Junctions; Heart Diseases; Humans; Myocardium; Myocytes, Cardiac; Nanotubes
PubMed: 34494646
DOI: 10.1242/bio.058777 -
Journal of Innate Immunity 2009
Topics: Animals; Cellular Structures; DNA; Extracellular Space; Humans; Immunoproteins; Mice; Neutrophil Activation; Neutrophils
PubMed: 20375574
DOI: 10.1159/000207015 -
Cell Death & Disease May 2013Although cell-in-cell structure was noted 100 years ago, the molecular mechanisms of 'entering' and the destination of cell-in-cell remain largely unclear. It takes... (Review)
Review
Although cell-in-cell structure was noted 100 years ago, the molecular mechanisms of 'entering' and the destination of cell-in-cell remain largely unclear. It takes place among the same type of cells (homotypic cell-in-cell) or different types of cells (heterotypic cell-in-cell). Cell-in-cell formation affects both effector cells and their host cells in multiple aspects, while cell-in-cell death is under more intensive investigation. Given that cell-in-cell has an important role in maintaining homeostasis, aberrant cell-in-cell process contributes to the etiopathology in humans. Indeed, cell-in-cell is observed in many pathological processes of human diseases. In this review, we intend to discuss the biological models of cell-in-cell structures under physiological and pathological status.
Topics: Cell Fusion; Cell Nucleus; Cell-in-Cell Formation; Humans; Lymphocytes; Models, Biological; Polyploidy
PubMed: 23681225
DOI: 10.1038/cddis.2013.147