scholarly journals The organisation and functions of local Ca2+ signals

2001 ◽  
Vol 114 (12) ◽  
pp. 2213-2222 ◽  
Author(s):  
Martin D. Bootman ◽  
Peter Lipp ◽  
Michael J. Berridge
Keyword(s):  
Cell Proliferation ◽  
Gene Transcription ◽  
Cell Biology ◽  
Building Blocks ◽  
Cell Types ◽  
Diverse Range ◽  
Cellular Processes ◽  
Different Cell Types ◽  
Intracellular Messenger ◽  
Sensory Mechanisms

Calcium (Ca2+) is a ubiquitous intracellular messenger, controlling a diverse range of cellular processes, such as gene transcription, muscle contraction and cell proliferation. The ability of a simple ion such as Ca2+ to play a pivotal role in cell biology results from the facility that cells have to shape Ca2+ signals in space, time and amplitude. To generate and interpret the variety of observed Ca2+ signals, different cell types employ components selected from a Ca2+ signalling ‘toolkit’, which comprises an array of homeostatic and sensory mechanisms. By mixing and matching components from the toolkit, cells can obtain Ca2+ signals that suit their physiology. Recent studies have demonstrated the importance of local Ca2+ signals in defining the specificity of the interaction of Ca2+ with its targets. Furthermore, local Ca2+ signals are the triggers and building blocks for larger global signals that propagate throughout cells.

scholarly journals A unified framework for inferring the multi-scale organization of chromatin domains from Hi-C

2019 ◽  
Author(s):  
Ji Hyun Bak ◽  
Min Hyeok Kim ◽  
Lei Liu ◽  
Changbong Hyeon
Keyword(s):  
Statistical Physics ◽  
Building Blocks ◽  
Cell Types ◽  
Unified Framework ◽  
Global Pattern ◽  
Chromatin Domains ◽  
Chromosome Conformation ◽  
Multi Scale ◽  
Unified Algorithm ◽  
Different Cell Types

AbstractIdentifying chromatin domains (CDs) from high-throughput chromosome conformation capture (Hi-C) data is currently a central problem in genome research. Here we present a unified algorithm, Multi-CD, which infers CDs at various genomic scales by leveraging the information from Hi-C. By integrating a model of the chromosome from polymer physics, statistical physics-based clustering analysis, and Bayesian inference, Multi-CD identifies the CDs that best represent the global pattern of correlation manifested in Hi-C. The multi-scale intra-chromosomal structures compared across different cell types allow us to glean the principles of chromatin organization: (i) Sub-TADs, TADs, and meta-TADs constitute a robust hierarchical structure. (ii) The assemblies of compartments and TAD-based domains are governed by different organizational principles. (iii) Sub-TADs are the common building blocks of chromosome architecture. CDs obtained from Multi-CD applied to Hi-C data enable a quantitative and comparative analysis of chromosome organization in different cell types, providing glimpses into structure-function relationship in genome.

scholarly journals miRNA-independent function of long noncoding pri-miRNA loci

2021 ◽  
Vol 118 (13) ◽  
pp. e2017562118
Author(s):  
Daniel He ◽  
David Wu ◽  
Soren Muller ◽  
Lin Wang ◽  
Parna Saha ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Cell Biology ◽  
Cell Types ◽  
Dna Looping ◽  
Gene Promoters ◽  
Functional Studies ◽  
A Genome ◽  
Genome Wide Data ◽  
Cell Propagation

Among the large, diverse set of mammalian long noncoding RNAs (lncRNAs), long noncoding primary microRNAs (lnc-pri-miRNAs) are those that host miRNAs. Whether lnc-pri-miRNA loci have important biological function independent of their cognate miRNAs is poorly understood. From a genome-scale lncRNA screen, lnc-pri-miRNA loci were enriched for function in cell proliferation, and in glioblastoma (i.e., GBM) cells with DGCR8 or DROSHA knockdown, lnc-pri-miRNA screen hits still regulated cell growth. To molecularly dissect the function of a lnc-pri-miRNA locus, we studied LOC646329 (also known as MIR29HG), which hosts the miR-29a/b1 cluster. In GBM cells, LOC646329 knockdown reduced miR-29a/b1 levels, and these cells exhibited decreased growth. However, genetic deletion of the miR-29a/b1 cluster (LOC646329-miR29Δ) did not decrease cell growth, while knockdown of LOC646329-miR29Δ transcripts reduced cell proliferation. The miR-29a/b1–independent activity of LOC646329 corresponded to enhancer-like activation of a neighboring oncogene (MKLN1), regulating cell propagation. The LOC646329 locus interacts with the MKLN1 promoter, and antisense oligonucleotide knockdown of the lncRNA disrupts these interactions and reduces the enhancer-like activity. More broadly, analysis of genome-wide data from multiple human cell types showed that lnc-pri-miRNA loci are significantly enriched for DNA looping interactions with gene promoters as well as genomic and epigenetic characteristics of transcriptional enhancers. Functional studies of additional lnc-pri-miRNA loci demonstrated cognate miRNA-independent enhancer-like activity. Together, these data demonstrate that lnc-pri-miRNA loci can regulate cell biology via both miRNA-dependent and miRNA-independent mechanisms.

scholarly journals JNK Signaling as a Key Modulator of Soft Connective Tissue Physiology, Pathology, and Healing

2020 ◽  
Vol 21 (3) ◽  
pp. 1015 ◽  
Author(s):  
Georgia Nikoloudaki ◽  
Sarah Brooks ◽  
Alexander P. Peidl ◽  
Dylan Tinney ◽  
Douglas W. Hamilton
Keyword(s):  
Wound Healing ◽  
Soft Tissue ◽  
Cell Biology ◽  
Soft Tissues ◽  
Tissue Injury ◽  
Cell Types ◽  
Cell Phenotype ◽  
Cell Behavior ◽  
Molecular Processes ◽  
Different Cell Types

In healthy individuals, the healing of soft tissues such as skin after pathological insult or post injury follows a relatively predictable and defined series of cell and molecular processes to restore tissue architecture and function(s). Healing progresses through the phases of hemostasis, inflammation, proliferation, remodeling, and concomitant with re-epithelialization restores barrier function. Soft tissue healing is achieved through the spatiotemporal interplay of multiple different cell types including neutrophils, monocytes/macrophages, fibroblasts, endothelial cells/pericytes, and keratinocytes. Expressed in most cell types, c-Jun N-terminal kinases (JNK) are signaling molecules associated with the regulation of several cellular processes involved in soft tissue wound healing and in response to cellular stress. A member of the mitogen-activated protein kinase family (MAPK), JNKs have been implicated in the regulation of inflammatory cell phenotype, as well as fibroblast, stem/progenitor cell, and epithelial cell biology. In this review, we discuss our understanding of JNKs in the regulation of cell behaviors related to tissue injury, pathology, and wound healing of soft tissues. Using models as diverse as Drosophila, mice, rats, as well as human tissues, research is now defining important, but sometimes conflicting roles for JNKs in the regulation of multiple molecular processes in multiple different cell types central to wound healing processes. In this review, we focus specifically on the role of JNKs in the regulation of cell behavior in the healing of skin, cornea, tendon, gingiva, and dental pulp tissues. We conclude that while parallels can be drawn between some JNK activities and the control of cell behavior in healing, the roles of JNK can also be very specific modes of action depending on the tissue and the phase of healing.

Gut epithelial IL-27 confers intestinal immunity through the induction of intraepithelial lymphocytes

2021 ◽  
Vol 218 (11) ◽  
Author(s):  
Chia-Hao Lin ◽  
Mei-Chi Chen ◽  
Ling-Li Lin ◽  
David A. Christian ◽  
Booki Min ◽  
...  
Keyword(s):  
Parasitic Infection ◽  
Cell Types ◽  
Functional Differentiation ◽  
Intraepithelial Lymphocytes ◽  
Intestinal Epithelial ◽  
Intestinal Immunity ◽  
Diverse Range ◽  
Pathogen Burden ◽  
Different Cell Types ◽  
Barrier Immunity

IL-27 controls a diverse range of immune responses in many disease settings. Here, we identify intestinal epithelial cells (IECs) as one of the major IL-27 cellular sources in the gut-associated tissue. Unlike IL-27 secreted by innate immune cells, gut epithelial IL-27 is dispensable for T-bet+ regulatory T cell (T reg cell) differentiation or IL-10 induction. Rather, IEC-derived IL-27 specifically promotes a distinct CD8αα+CD4+ intraepithelial lymphocyte (IEL) population that acquires their functional differentiation at the intestinal epithelium. Loss of IL-27 in IECs leads to a selective defect in CD8αα+CD4+ IELs over time. Consequently, mice with IEC-specific IL-27 ablation exhibited elevated pathogen burden during parasitic infection, and this could be rescued by transfer of exogenous CD8αα+CD4+ IELs. Collectively, our data reveal that in addition to its known regulatory properties in preventing immune hyperactivity, gut epithelial IL-27 confers barrier immunity by inducing a specific IEL subset and further suggest that IL-27 produced by different cell types plays distinct roles in maintaining intestinal homeostasis.

Targeting of membrane transporters in renal epithelia: when cell biology meets physiology

2000 ◽  
Vol 278 (2) ◽  
pp. F192-F201 ◽  
Author(s):  
Dennis Brown
Keyword(s):  
Epithelial Cells ◽  
Cell Biology ◽  
Cell Types ◽  
Coat Proteins ◽  
Membrane Domains ◽  
Cellular Functions ◽  
Sorting Signals ◽  
The Many ◽  
Different Cell Types

Epithelial cells in the kidney have highly specialized transport mechanisms that differ among the many tubule segments, and among the different cell types that are present in some regions. The purpose of this brief review is to examine some of the major intracellular mechanisms by which the membrane proteins that participate in these differentiated cellular functions are addressed, sorted, and delivered to specific membrane domains of epithelial cells. Unraveling these processes is important not only for our understanding of normal cellular function but is also critical for the interpretation of pathophysiological dysfunction in the context of newly generated molecular and cellular information concerning hereditary and acquired transporter abnormalities. Among the topics covered are sorting signals on proteins, role of the cytoskeleton, vesicle coat proteins, the fusion machinery, and exo- and endocytosis of recycling proteins. Examples of these events in renal epithelial cells are highlighted throughout this review and are related to the physiology of the kidney.

scholarly journals Membrane mechanics govern spatiotemporal heterogeneity of endocytic clathrin coat dynamics

2017 ◽  
Vol 28 (24) ◽  
pp. 3480-3488 ◽  
Author(s):  
N. M. Willy ◽  
J. P. Ferguson ◽  
S. D. Huber ◽  
S. P. Heidotting ◽  
E. Aygün ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Morphological Changes ◽  
Cell Types ◽  
Membrane Tension ◽  
Membrane Mechanics ◽  
Cellular Processes ◽  
Spatiotemporal Heterogeneity ◽  
Multicellular Organisms ◽  
Different Cell Types

Dynamics of endocytic clathrin-coated structures can be remarkably divergent across different cell types, cells within the same culture, or even distinct surfaces of the same cell. The origin of this astounding heterogeneity remains to be elucidated. Here we show that cellular processes associated with changes in effective plasma membrane tension induce significant spatiotemporal alterations in endocytic clathrin coat dynamics. Spatiotemporal heterogeneity of clathrin coat dynamics is also observed during morphological changes taking place within developing multicellular organisms. These findings suggest that tension gradients can lead to patterning and differentiation of tissues through mechanoregulation of clathrin-mediated endocytosis.

Neuronal Diversity In The Retina

e-Neuroforum ◽  
2017 ◽  
Vol 23 (2) ◽  
Author(s):  
Philipp Berens ◽  
Thomas Euler
Keyword(s):  
Building Blocks ◽  
Cell Types ◽  
Relevant Information ◽  
Future Research ◽  
Neuronal Diversity ◽  
Form Complex ◽  
Current State ◽  
Complex Circuits ◽  
Different Cell Types ◽  
The Brain

AbstractThe retina in the eye performs complex computations, to transmit only behaviourally relevant information about our visual environment to the brain. These computations are implemented by numerous different cell types that form complex circuits. New experimental and computational methods make it possible to study the cellular diversity of the retina in detail – the goal of obtaining a complete list of all the cell types in the retina and, thus, its “building blocks”, is within reach. We review the current state of this endeavour and highlight possible directions for future research.

scholarly journals A modular microfluidic bioreactor to investigate plant cell–cell interactions

PROTOPLASMA ◽  
2021 ◽  
Author(s):  
T. Finkbeiner ◽  
C. Manz ◽  
M. L. Raorane ◽  
C. Metzger ◽  
L. Schmidt-Speicher ◽  
...  
Keyword(s):  
Plant Cell ◽  
Cell Biology ◽  
Cultured Cells ◽  
Abiotic Factors ◽  
Welding Process ◽  
Cell Types ◽  
Cell Interactions ◽  
Chemical Signalling ◽  
Different Cell Types ◽  
Cell Cell

AbstractPlants produce a wide variety of secondary metabolites, which often are of interest to pharmaceutical and nutraceutical industry. Plant-cell cultures allow producing these metabolites in a standardised manner, independently from various biotic and abiotic factors difficult to control during conventional cultivation. However, plant-cell fermentation proves to be very difficult, since these chemically complex compounds often result from the interaction of different biosynthetic pathways operating in different cell types. To simulate such interactions in cultured cells is a challenge. Here, we present a microfluidic bioreactor for plant-cell cultivation to mimic the cell–cell interactions occurring in real plant tissues. In a modular set-up of several microfluidic bioreactors, different cell types can connect through a flow that transports signals or metabolites from module to module. The fabrication of the chip includes hot embossing of a polycarbonate housing and subsequent integration of a porous membrane and in-plane tube fittings in a two-step ultrasonic welding process. The resulting microfluidic chip is biocompatible and transparent. Simulation of mass transfer for the nutrient sucrose predicts a sufficient nutrient supply through the membrane. We demonstrate the potential of this chip for plant cell biology in three proof-of-concept applications. First, we use the chip to show that tobacco BY-2 cells in suspension divide depending on a “quorum-sensing factor” secreted by proliferating cells. Second, we show that a combination of two Catharanthus roseus cell strains with complementary metabolic potency allows obtaining vindoline, a precursor of the anti-tumour compound vincristine. Third, we extend the approach to operationalise secretion of phytotoxins by the fungus Neofusicoccum parvum as a step towards systems to screen for interorganismal chemical signalling.

scholarly journals The Multiple Faces of MNT and Its Role as a MYC Modulator

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4682
Author(s):  
Judit Liaño-Pons ◽  
Marie Arsenian-Henriksson ◽  
Javier León
Keyword(s):  
Cell Proliferation ◽  
Transcriptional Repression ◽  
Cell Biology ◽  
Essential Role ◽  
Present Knowledge ◽  
Special Focus ◽  
Cellular Functions ◽  
Cellular Processes ◽  
Tumor Cell Survival

MNT is a crucial modulator of MYC, controls several cellular functions, and is activated in most human cancers. It is the largest, most divergent, and most ubiquitously expressed protein of the MXD family. MNT was first described as a MYC antagonist and tumor suppressor. Indeed, 10% of human tumors present deletions of one MNT allele. However, some reports show that MNT functions in cooperation with MYC by maintaining cell proliferation, promoting tumor cell survival, and supporting MYC-driven tumorigenesis in cellular and animal models. Although MAX was originally considered MNT’s obligate partner, our recent findings demonstrate that MNT also works independently. MNT forms homodimers and interacts with proteins both outside and inside of the proximal MYC network. These complexes are involved in a wide array of cellular processes, from transcriptional repression via SIN3 to the modulation of metabolism through MLX as well as immunity and apoptosis via REL. In this review, we discuss the present knowledge of MNT with a special focus on its interactome, which sheds light on the complex and essential role of MNT in cell biology.

scholarly journals Functional annotation of lncRNA in high-throughput screening

2021 ◽  
Author(s):  
Chi Wai Yip ◽  
Divya M. Sivaraman ◽  
Anika V. Prabhu ◽  
Jay W. Shin
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Functional Annotation ◽  
Cell Types ◽  
Specific Expression ◽  
Functional Roles ◽  
Cellular Processes ◽  
Cell Type Specific Expression ◽  
Cell Type Specific ◽  
Different Cell Types

Abstract Recent efforts on the characterization of long non-coding RNAs (lncRNAs) revealed their functional roles in modulating diverse cellular processes. These include pluripotency maintenance, lineage commitment, carcinogenesis, and pathogenesis of various diseases. By interacting with DNA, RNA and protein, lncRNAs mediate multifaceted mechanisms to regulate transcription, RNA processing, RNA interference and translation. Of more than 173000 discovered lncRNAs, the majority remain functionally unknown. The cell type-specific expression and localization of the lncRNA also suggest potential distinct functions of lncRNAs across different cell types. This highlights the niche of identifying functional lncRNAs in different biological processes and diseases through high-throughput (HTP) screening. This review summarizes the current work performed and perspectives on HTP screening of functional lncRNAs where different technologies, platforms, cellular responses and the downstream analyses are discussed. We hope to provide a better picture in applying different technologies to facilitate functional annotation of lncRNA efficiently.

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