scholarly journals Review of the Isolation, Characterization, Biological Function, and Multifarious Therapeutic Approaches of Exosomes

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 307 ◽  
Author(s):  
Sangiliyandi Gurunathan ◽  
Min-Hee Kang ◽  
Muniyandi Jeyaraj ◽  
Muhammad Qasim ◽  
Jin-Hoi Kim
Keyword(s):  
Molecular Mechanisms ◽  
Cell Communication ◽  
Biological Functions ◽  
Research Attention ◽  
Diagnosis And Prognosis ◽  
Imaging Probes ◽  
Health And Disease ◽  
The Stability ◽  
And Function ◽  
Invasive Diagnostics

Exosomes are extracellular vesicles that contain a specific composition of proteins, lipids, RNA, and DNA. They are derived from endocytic membranes and can transfer signals to recipient cells, thus mediating a novel mechanism of cell-to-cell communication. They are also thought to be involved in cellular waste disposal. Exosomes play significant roles in various biological functions, including the transfer of biomolecules such as RNA, proteins, enzymes, and lipids and the regulation of numerous physiological and pathological processes in various diseases. Because of these properties, they are considered to be promising biomarkers for the diagnosis and prognosis of various diseases and may contribute to the development of minimally invasive diagnostics and next generation therapies. The biocompatible nature of exosomes could enhance the stability and efficacy of imaging probes and therapeutics. Due to their potential use in clinical applications, exosomes have attracted much research attention on their roles in health and disease. To explore the use of exosomes in the biomedical arena, it is essential that the basic molecular mechanisms behind the transport and function of these vesicles are well-understood. Herein, we discuss the history, biogenesis, release, isolation, characterization, and biological functions of exosomes, as well as the factors influencing their biogenesis and their technical and biological challenges. We conclude this review with a discussion on the future perspectives of exosomes.

GAMYB TF modulates bHLH142 and is homeostatically regulated by TDR TF during rice anther tapetal and pollen development

2021 ◽  
Author(s):  
Swee-Suak Ko ◽  
Min-Jeng Li ◽  
Yi-Cheng Ho ◽  
Chun-Ping Yu ◽  
Ting-Ting Yang ◽  
...  
Keyword(s):  
Pollen Development ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Specific Binding ◽  
Biological Functions ◽  
Altered Expression ◽  
Regulatory Pathways ◽  
E Box ◽  
And Function ◽  
Different Tissues

Abstract GAMYB, UDT1, TIP2/bHLH142, TDR, and EAT1/DTD are important transcription factors (TFs) that play a crucial role during rice pollen development. This study demonstrates that bHLH142 acts downstream of UDT1 and GAMYB and works as a “hub” in these two pollen pathways. We show that GAMYB modulates bHLH142 expression through specific binding to the MYB motif of bHLH142 promoter during early stage of pollen development; while TDR acts as a transcriptional repressor of the GAMYB modulation of bHLH142 by binding to the E-box close to the MYB motif on the promoter. The altered expression of TFs highlights the importance that a tight, precise, and coordinated regulation among these TFs is essential for normal pollen development. Most notably, this study illustrates the regulatory pathways of GAMYB and UDT1 that rely on bHLH142 in a direct and an indirect manner, respectively, and function in different tissues with distinct biological functions during pollen development. This study advances our understanding of the molecular mechanisms of rice pollen development.

scholarly journals The Glycine Lipids ofBacteroides thetaiotaomicronAre Important for Fitness during GrowthIn VivoandIn Vitro

2018 ◽  
Vol 85 (10) ◽  
Author(s):  
Alli Lynch ◽  
Seshu R. Tammireddy ◽  
Mary K. Doherty ◽  
Phillip D. Whitfield ◽  
David J. Clarke
Keyword(s):  
Amino Acid ◽  
Gut Microbiome ◽  
Molecular Mechanisms ◽  
Cellular Membrane ◽  
Bacteroides Thetaiotaomicron ◽  
Human Gut ◽  
Acyltransferase Activity ◽  
Content Type ◽  
Health And Disease ◽  
And Function

ABSTRACTAcylated amino acids function as important components of the cellular membrane in some bacteria. Biosynthesis is initiated by theN-acylation of the amino acid, and this is followed by subsequentO-acylation of the acylated molecule, resulting in the production of the mature diacylated amino acid lipid. In this study, we use both genetics and liquid chromatography-mass spectrometry (LC-MS) to characterize the biosynthesis and function of a diacylated glycine lipid (GL) species produced inBacteroides thetaiotaomicron. We, and others, have previously reported the identification of a gene, namedglsBin this study, that encodes anN-acyltransferase activity responsible for the production of a monoacylated glycine calledN-acyl-3-hydroxy-palmitoyl glycine (or commendamide). In all of theBacteroidalesgenomes sequenced so far, theglsBgene is located immediately downstream from a gene, namedglsA, that is also predicted to encode a protein with acyltransferase activity. We use LC-MS to show that the coexpression ofglsBandglsAresults in the production of GL inEscherichia coli. We constructed a deletion mutant of theglsBgene inB. thetaiotaomicron, and we confirm thatglsBis required for the production of GL inB. thetaiotaomicron. Moreover, we show thatglsBis important for the ability ofB. thetaiotaomicronto adapt to stress and colonize the mammalian gut. Therefore, this report describes the genetic requirements for the biosynthesis of GL, a diacylated amino acid species that contributes to fitness in the human gut bacteriumB. thetaiotaomicron.IMPORTANCEThe gut microbiome has an important role in both health and disease of the host. The mammalian gut microbiome is often dominated by bacteria from theBacteroidales, an order that includesBacteroidesandPrevotella. In this study, we have identified an acylated amino acid, called glycine lipid, produced byBacteroides thetaiotaomicron, a beneficial bacterium originally isolated from the human gut. In addition to identifying the genes required for the production of glycine lipids, we show that glycine lipids have an important role during the adaptation ofB. thetaiotaomicronto a number of environmental stresses, including exposure to either bile or air. We also show that glycine lipids are important for the normal colonization of the murine gut byB. thetaiotaomicron. This work identifies glycine lipids as an important fitness determinant inB. thetaiotaomicronand therefore increases our understanding of the molecular mechanisms underpinning colonization of the mammalian gut by beneficial bacteria.

scholarly journals Mitochondrial Iron in Human Health and Disease

2019 ◽  
Vol 81 (1) ◽  
pp. 453-482 ◽  
Author(s):  
Diane M. Ward ◽  
Suzanne M. Cloonan
Keyword(s):  
Human Health ◽  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Innate Immune ◽  
Biological Functions ◽  
Mitochondrial Homeostasis ◽  
Innate Immune Signaling ◽  
Mitochondrial Iron ◽  
Health And Disease

Mitochondria are an iconic distinguishing feature of eukaryotic cells. Mitochondria encompass an active organellar network that fuses, divides, and directs a myriad of vital biological functions, including energy metabolism, cell death regulation, and innate immune signaling in different tissues. Another crucial and often underappreciated function of these dynamic organelles is their central role in the metabolism of the most abundant and biologically versatile transition metals in mammalian cells, iron. In recent years, cellular and animal models of mitochondrial iron dysfunction have provided vital information in identifying new proteins that have elucidated the pathways involved in mitochondrial homeostasis and iron metabolism. Specific signatures of mitochondrial iron dysregulation that are associated with disease pathogenesis and/or progression are becoming increasingly important. Understanding the molecular mechanisms regulating mitochondrial iron pathways will help better define the role of this important metal in mitochondrial function and in human health and disease.

scholarly journals A comprehensive guide to the ROMK potassium channel: form and function in health and disease

2009 ◽  
Vol 297 (4) ◽  
pp. F849-F863 ◽  
Author(s):  
Paul A. Welling ◽  
Kevin Ho
Keyword(s):  
Potassium Channel ◽  
Molecular Mechanisms ◽  
Atomic Level ◽  
Structural Basis ◽  
Potassium Homeostasis ◽  
Form And Function ◽  
Founding Member ◽  
Channel Form ◽  
Health And Disease ◽  
And Function

The discovery of the renal outer medullary K+channel (ROMK, Kir1.1), the founding member of the inward-rectifying K+channel (Kir) family, by Ho and Hebert in 1993 revolutionized our understanding of potassium channel biology and renal potassium handling. Because of the central role that ROMK plays in the regulation of salt and potassium homeostasis, considerable efforts have been invested in understanding the underlying molecular mechanisms. Here we provide a comprehensive guide to ROMK, spanning from the physiology in the kidney to the organization and regulation by intracellular factors to the structural basis of its function at the atomic level.

scholarly journals Unique structural features of the mitochondrial AAA+ protease AFG3L2 reveal the molecular basis for activity in health and disease

2019 ◽  
Author(s):  
Cristina Puchades ◽  
Bojian Ding ◽  
Albert Song ◽  
R. Luke Wiseman ◽  
Gabriel C. Lander ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Structural Data ◽  
Structural Features ◽  
Genetic Mutations ◽  
Biological Functions ◽  
Catalytic Core ◽  
Structural Framework ◽  
Health And Disease

AbstractMitochondrial AAA+ quality control proteases regulate diverse aspects of mitochondrial biology through specialized protein degradation, but the underlying molecular mechanisms that define the diverse activities of these enzymes remain poorly defined. The mitochondrial AAA+ protease AFG3L2 is of particular interest, as genetic mutations localized throughout AFG3L2 are linked to diverse neurodegenerative disorders. However, a lack of structural data has limited our understanding of how mutations impact enzymatic activity. Here, we used cryo-EM to determine a substrate-bound structure of the catalytic core of human AFG3L2. This structure identifies multiple specialized structural features within AFG3L2 that integrate with conserved structural motifs required for hand-over-hand ATP-dependent substrate translocation to engage, unfold and degrade targeted proteins. Mapping disease-relevant AFG3L2 mutations onto our structure demonstrates that many of these mutations localize to these unique structural features of AFG3L2 and distinctly influence its activity and stability. Our results provide a molecular basis for neurological phenotypes associated with different AFG3L2 mutations, and establish a structural framework to understand how different members of the AAA+ superfamily achieve specialized, diverse biological functions.

scholarly journals Role of Choline in Ocular Diseases

2021 ◽  
Vol 22 (9) ◽  
pp. 4733
Author(s):  
Jin-Sun Hwang ◽  
Young-Joo Shin
Keyword(s):  
Parasympathetic Nervous System ◽  
Retinal Hemorrhage ◽  
Ocular Diseases ◽  
Choline Deficiency ◽  
Eye Health ◽  
Development And Differentiation ◽  
Health And Disease ◽  
The Stability ◽  
And Function

Choline is essential for maintaining the structure and function of cells in humans. Choline plays an important role in eye health and disease. It is a precursor of acetylcholine, a neurotransmitter of the parasympathetic nervous system, and it is involved in the production and secretion of tears by the lacrimal glands. It also contributes to the stability of the cells and tears on the ocular surface and is involved in retinal development and differentiation. Choline deficiency is associated with retinal hemorrhage, glaucoma, and dry eye syndrome. Choline supplementation may be effective for treating these diseases.

scholarly journals Cartilage to bone transitions in health and disease

2013 ◽  
Vol 219 (1) ◽  
pp. R1-R12 ◽  
Author(s):  
K A Staines ◽  
A S Pollard ◽  
I M McGonnell ◽  
C Farquharson ◽  
A A Pitsillides
Keyword(s):  
Molecular Mechanisms ◽  
Bone Development ◽  
Postnatal Growth ◽  
Current Evidence ◽  
Future Research ◽  
Physiological Mechanisms ◽  
Disease Aetiology ◽  
Health And Disease ◽  
Transient Events ◽  
And Function

Aberrant redeployment of the ‘transient’ events responsible for bone development and postnatal longitudinal growth has been reported in some diseases in what is otherwise inherently ‘stable’ cartilage. Lessons may be learnt from the molecular mechanisms underpinning transient chondrocyte differentiation and function, and their application may better identify disease aetiology. Here, we review the current evidence supporting this possibility. We firstly outline endochondral ossification and the cellular and physiological mechanisms by which it is controlled in the postnatal growth plate. We then compare the biology of these transient cartilaginous structures to the inherently stable articular cartilage. Finally, we highlight specific scenarios in which the redeployment of these embryonic processes may contribute to disease development, with the foresight that deciphering those mechanisms regulating pathological changes and loss of cartilage stability will aid future research into effective disease-modifying therapies.

scholarly journals Neddylation, an Emerging Mechanism Regulating Cardiac Development and Function

2020 ◽  
Vol 11 ◽  
Author(s):  
Jie Li ◽  
Jianqiu Zou ◽  
Rodney Littlejohn ◽  
Jinbao Liu ◽  
Huabo Su
Keyword(s):  
Quality Control ◽  
Protein Quality ◽  
Cardiac Development ◽  
Current Knowledge ◽  
Biological Significance ◽  
Protein Quality Control ◽  
Pathogenic Factors ◽  
Health And Disease ◽  
The Stability ◽  
And Function

Defects in protein quality control have been increasingly recognized as pathogenic factors in the development of heart failure, a persistent devastating disease lacking efficacious therapies. Ubiquitin and ubiquitin-like proteins, a family of post-translational modifying polypeptides, play important roles in controlling protein quality by maintaining the stability and functional diversity of the proteome. NEDD8 (neural precursor cell expressed, developmentally downregulated 8), a small ubiquitin-like protein, was discovered two decades ago but until recently the biological significance of NEDD8 modifications (neddylation) in the heart has not been appreciated. In this review, we summarize the current knowledge of the biology of neddylation, highlighting several mechanisms by which neddylation regulates the function of its downstream targets, and discuss the expanding roles for neddylation in cardiac physiology and disease, with an emphasis on cardiac protein quality control. Finally, we outline challenges linked to the study of neddylation in health and disease.

Tunneling nanotubes and related structures: molecular mechanisms of formation and function

2021 ◽  
Vol 478 (22) ◽  
pp. 3977-3998
Author(s):  
Sunayana Dagar ◽  
Diksha Pathak ◽  
Harsh V. Oza ◽  
Sivaram V. S. Mylavarapu
Keyword(s):  
Molecular Motors ◽  
Actin Polymerization ◽  
Molecular Mechanisms ◽  
Cell Communication ◽  
Microbial Pathogens ◽  
Actin Dynamics ◽  
Cortical Actin ◽  
Animal Cells ◽  
Tunneling Nanotubes ◽  
And Function

Tunneling nanotubes (TNTs) are F-actin-based, membrane-enclosed tubular connections between animal cells that transport a variety of cellular cargo. Over the last 15 years since their discovery, TNTs have come to be recognized as key players in normal cell communication and organism development, and are also exploited for the spread of various microbial pathogens and major diseases like cancer and neurodegenerative disorders. TNTs have also been proposed as modalities for disseminating therapeutic drugs between cells. Despite the rapidly expanding and wide-ranging relevance of these structures in both health and disease, there is a glaring dearth of molecular mechanistic knowledge regarding the formation and function of these important but enigmatic structures. A series of fundamental steps are essential for the formation of functional nanotubes. The spatiotemporally controlled and directed modulation of cortical actin dynamics would be required to ensure outward F-actin polymerization. Local plasma membrane deformation to impart negative curvature and membrane addition at a rate commensurate with F-actin polymerization would enable outward TNT elongation. Extrinsic tactic cues, along with cognate intrinsic signaling, would be required to guide and stabilize the elongating TNT towards its intended target, followed by membrane fusion to create a functional TNT. Selected cargoes must be transported between connected cells through the action of molecular motors, before the TNT is retracted or destroyed. This review summarizes the current understanding of the molecular mechanisms regulating these steps, also highlighting areas that deserve future attention.

Musculoskeletal complications associated with pathological iron toxicity and its molecular mechanisms

2021 ◽  
Vol 49 (2) ◽  
pp. 747-759
Author(s):  
Márcio Simão ◽  
M. Leonor Cancela
Keyword(s):  
Tissue Regeneration ◽  
Molecular Mechanisms ◽  
Negative Impact ◽  
Life Quality ◽  
Cell Communication ◽  
Iron Toxicity ◽  
Hereditary Diseases ◽  
Biological Functions ◽  
Intracellular Iron ◽  
Susceptibility Factors

Iron is fundamental for several biological functions, but when in excess can lead to the development of toxic events. Some tissues and cells are more susceptible than others, but systemic iron levels can be controlled by treating patients with iron-chelating molecules and phlebotomy. An early diagnostic can be decisive to limit the progression of musculoskeletal complications like osteoarthritis and osteoporosis because of iron toxicity. In iron-related osteoarthritis, aggravation can be associated to a few events that can contribute to joints articular cartilage exposure to high iron concentrations, which can promote articular degeneration with very little chance of tissue regeneration. In contrast, bone metabolism is much more dynamic than cartilage, but progressive iron accumulation and ageing can be decisive factors for bone health. The iron overload associated with hereditary diseases like hemochromatosis, hemophilias, thalassemias and other hereditary anaemias increase the negative impact of iron toxicity in joints and bone, as well as in life quality, even when iron levels can be controlled. The molecular mechanisms by which iron can compromise cartilage and bone have been illusive and only in the last 20 years studies have started to shed some light into the molecular mechanisms associated with iron toxicity. Ferroptosis and the regulation of intracellular iron levels is instrumental in the balance between detoxification and induced cell death. In addition, these complications are accompanied with multiple susceptibility factors that can aggravate iron toxicity and should be identified. Therefore, understanding tissues microenvironment and cell communication is fundamental to contextualize iron toxicity.

Sign in / Sign up

Export Citation Format

Share Document