scholarly journals The “Stressful” Life of Cell Adhesion Molecules: On the Mechanosensitivity of Integrin Adhesome

2018 ◽  
Vol 140 (2) ◽  
Author(s):  
Hengameh Shams ◽  
Brenton D. Hoffman ◽  
Mohammad R. K. Mofrad
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Mechanical Energy ◽  
Focal Adhesions ◽  
Local Stress ◽  
Local Composition ◽  
Functional Changes ◽  
Cellular Processes ◽  
Biochemical Pathways ◽  
Mechanochemical Signaling

Cells have evolved into complex sensory machines that communicate with their microenvironment via mechanochemical signaling. Extracellular mechanical cues trigger complex biochemical pathways in the cell, which regulate various cellular processes. Integrin-mediated focal adhesions (FAs) are large multiprotein complexes, also known as the integrin adhesome, that link the extracellular matrix (ECM) to the actin cytoskeleton, and are part of powerful intracellular machinery orchestrating mechanotransduction pathways. As forces are transmitted across FAs, individual proteins undergo structural and functional changes that involve a conversion of chemical to mechanical energy. The local composition of early adhesions likely defines the regional stress levels and determines the type of newly recruited proteins, which in turn modify the local stress distribution. Various approaches have been used for detecting and exploring molecular mechanisms through which FAs are spatiotemporally regulated, however, many aspects are yet to be understood. Current knowledge on the molecular mechanisms of mechanosensitivity in adhesion proteins is discussed herein along with important questions yet to be addressed, are discussed.

scholarly journals The Chinese Medicinal Formulation Guzhi Zengsheng Zhitongwan Modulates Chondrocyte Structure, Dynamics, and Metabolism by Controlling Multiple Functional Proteins

2018 ◽  
Vol 2018 ◽  
pp. 1-12
Author(s):  
Baojin Yao ◽  
Bocheng Lu ◽  
Mei Zhang ◽  
Hongwei Gao ◽  
Xiangyang Leng ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Research Field ◽  
Medical Systems ◽  
Cellular Processes ◽  
Structure Dynamics ◽  
National Medical ◽  
Medicinal Formulation

Traditional Chinese medicine is one of the oldest medical systems in the world and has its unique principles and theories in the prevention and treatment of human diseases, which are achieved through the interactions of different types of materia medica in the form of Chinese medicinal formulations. GZZSZTW, a classical and effective Chinese medicinal formulation, was designed and created by professor Bailing Liu who is the only national medical master professor in the clinical research field of traditional Chinese medicine and skeletal diseases. GZZSZTW has been widely used in clinical settings for several decades for the treatment of joint diseases. However, the underlying molecular mechanisms are still largely unknown. In the present study, we performed quantitative proteomic analysis to investigate the effects of GZZSZTW on mouse primary chondrocytes using state-of-the-art iTRAQ technology. We demonstrated that the Chinese medicinal formulation GZZSZTW modulates chondrocyte structure, dynamics, and metabolism by controlling multiple functional proteins that are involved in the cellular processes of DNA replication and transcription, protein synthesis and degradation, cytoskeleton dynamics, and signal transduction. Thus, this study has expanded the current knowledge of the molecular mechanism of GZZSZTW treatment on chondrocytes. It has also shed new light on possible strategies to further prevent and treat cartilage-related diseases using traditional Chinese medicinal formulations.

scholarly journals Lysosomal Exocytosis, Exosome Release and Secretory Autophagy: The Autophagic- and Endo-Lysosomal Systems Go Extracellular

2020 ◽  
Vol 21 (7) ◽  
pp. 2576 ◽  
Author(s):  
Sandra Buratta ◽  
Brunella Tancini ◽  
Krizia Sagini ◽  
Federica Delo ◽  
Elisabetta Chiaradia ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Cell Communication ◽  
Lysosomal Storage ◽  
Cellular Processes ◽  
Age Related ◽  
Extracellular Release ◽  
A Cell ◽  
Endosomal System

Beyond the consolidated role in degrading and recycling cellular waste, the autophagic- and endo-lysosomal systems play a crucial role in extracellular release pathways. Lysosomal exocytosis is a process leading to the secretion of lysosomal content upon lysosome fusion with plasma membrane and is an important mechanism of cellular clearance, necessary to maintain cell fitness. Exosomes are a class of extracellular vesicles originating from the inward budding of the membrane of late endosomes, which may not fuse with lysosomes but be released extracellularly upon exocytosis. In addition to garbage disposal tools, they are now considered a cell-to-cell communication mechanism. Autophagy is a cellular process leading to sequestration of cytosolic cargoes for their degradation within lysosomes. However, the autophagic machinery is also involved in unconventional protein secretion and autophagy-dependent secretion, which are fundamental mechanisms for toxic protein disposal, immune signalling and pathogen surveillance. These cellular processes underline the crosstalk between the autophagic and the endosomal system and indicate an intersection between degradative and secretory functions. Further, they suggest that the molecular mechanisms underlying fusion, either with lysosomes or plasma membrane, are key determinants to maintain cell homeostasis upon stressing stimuli. When they fail, the accumulation of undigested substrates leads to pathological consequences, as indicated by the involvement of autophagic and lysosomal alteration in human diseases, namely lysosomal storage disorders, age-related neurodegenerative diseases and cancer. In this paper, we reviewed the current knowledge on the functional role of extracellular release pathways involving lysosomes and the autophagic- and endo-lysosomal systems, evaluating their implication in health and disease.

scholarly journals Chromatin dynamics during interphase and cell division: similarities and differences between model and crop plants

2019 ◽  
Vol 71 (17) ◽  
pp. 5205-5222 ◽  
Author(s):  
Ales Pecinka ◽  
Christian Chevalier ◽  
Isabelle Colas ◽  
Kriton Kalantidis ◽  
Serena Varotto ◽  
...  
Keyword(s):  
Genetic Information ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Crop Plants ◽  
Regulatory Proteins ◽  
Abiotic And Biotic Stresses ◽  
Chromatin Dynamics ◽  
Biotic Stresses ◽  
Cellular Processes ◽  
Organismal Development

Abstract Genetic information in the cell nucleus controls organismal development and responses to the environment, and finally ensures its own transmission to the next generations. To achieve so many different tasks, the genetic information is associated with structural and regulatory proteins, which orchestrate nuclear functions in time and space. Furthermore, plant life strategies require chromatin plasticity to allow a rapid adaptation to abiotic and biotic stresses. Here, we summarize current knowledge on the organization of plant chromatin and dynamics of chromosomes during interphase and mitotic and meiotic cell divisions for model and crop plants differing as to genome size, ploidy, and amount of genomic resources available. The existing data indicate that chromatin changes accompany most (if not all) cellular processes and that there are both shared and unique themes in the chromatin structure and global chromosome dynamics among species. Ongoing efforts to understand the molecular mechanisms involved in chromatin organization and remodeling have, together with the latest genome editing tools, potential to unlock crop genomes for innovative breeding strategies and improvements of various traits.

scholarly journals Molecular and Cellular Mechanisms Modulating Trained Immunity by Various Cell Types in Response to Pathogen Encounter

2021 ◽  
Vol 12 ◽  
Author(s):  
Orlando A. Acevedo ◽  
Roslye V. Berrios ◽  
Linmar Rodríguez-Guilarte ◽  
Bastián Lillo-Dapremont ◽  
Alexis M. Kalergis
Keyword(s):  
Immune Cells ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Tca Cycle ◽  
Cell Types ◽  
Innate Immune ◽  
Epigenetic Changes ◽  
Cellular Mechanisms ◽  
Functional Changes ◽  
Trained Immunity

The induction of trained immunity represents an emerging concept defined as the ability of innate immune cells to acquire a memory phenotype, which is a typical hallmark of the adaptive response. Key points modulated during the establishment of trained immunity include epigenetic, metabolic and functional changes in different innate-immune and non-immune cells. Regarding to epigenetic changes, it has been described that long non-coding RNAs (LncRNAs) act as molecular scaffolds to allow the assembly of chromatin-remodeling complexes that catalyze epigenetic changes on chromatin. On the other hand, relevant metabolic changes that occur during this process include increased glycolytic rate and the accumulation of metabolites from the tricarboxylic acid (TCA) cycle, which subsequently regulate the activity of histone-modifying enzymes that ultimately drive epigenetic changes. Functional consequences of established trained immunity include enhanced cytokine production, increased antigen presentation and augmented antimicrobial responses. In this article, we will discuss the current knowledge regarding the ability of different cell subsets to acquire a trained immune phenotype and the molecular mechanisms involved in triggering such a response. This knowledge will be helpful for the development of broad-spectrum therapies against infectious diseases based on the modulation of epigenetic and metabolic cues regulating the development of trained immunity.

Targeting of Rab GTPases to cellular membranes

2005 ◽  
Vol 33 (4) ◽  
pp. 652-656 ◽  
Author(s):  
B.R. Ali ◽  
M.C. Seabra
Keyword(s):  
Membrane Trafficking ◽  
Cellular Localization ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Small Gtpases ◽  
Rab Proteins ◽  
Rab Gtpases ◽  
Cellular Membranes ◽  
Structural Determinants ◽  
Cellular Processes

Rab proteins are members of the superfamily of Ras-like small GTPases and are involved in several cellular processes relating to membrane trafficking and organelle mobility throughout the cell. Like other small GTPases, Rab proteins are initially synthesized as soluble proteins and for membrane attachment they require the addition of lipid moiety(ies) to specific residues of their polypeptide chain. Despite their well-documented roles in regulating cellular trafficking, Rab proteins own trafficking is still poorly understood. We still need to elucidate the molecular mechanisms of their recruitment to cellular membranes and the structural determinants for their specific cellular localization. Recent results indicate that Rab cellular targeting might be Rab-dependent, and this paper briefly reviews our current knowledge of this process.

scholarly journals Non-coding RNA Regulated Cross-Talk Between Mitochondria and Other Cellular Compartments

2021 ◽  
Vol 9 ◽  
Author(s):  
Jinliang Huang ◽  
Sipeng Wu ◽  
Pengcheng Wang ◽  
Geng Wang
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Mitochondrial Gene ◽  
Cellular Energy ◽  
Cellular Processes ◽  
Non Coding Rna ◽  
Mitochondrial Biosynthesis ◽  
Non Coding Rnas ◽  
Functional States ◽  
Cellular Compartments

Mitochondria are the main hubs for cellular energy production. Metabolites produced in mitochondria not only feed many important biosynthesis pathways but also function as signaling molecules. Mitochondrial biosynthesis requires collaboration of both nuclear and mitochondrial gene expression systems. In addition, mitochondria have to quickly respond to changes inside and outside the cells and have their own functional states reported to the nucleus and other cellular compartments. The underlying molecular mechanisms of these complex regulations have not been well understood. Recent evidence indicates that in addition to small molecules, non-coding RNAs may contribute to the communication between mitochondria and other cellular compartments and may even serve as signals. In this review, we summarize the current knowledge about mitochondrial non-coding RNAs (including nucleus-encoded non-coding RNAs that are imported into mitochondria and mitochondrion-encoded non-coding RNAs that are exported), their trafficking and their functions in co-regulation of mitochondrial and other cellular processes.

Multitalented actors inside and outside the cell: recent discoveries add to the number of moonlighting proteins

2019 ◽  
Vol 47 (6) ◽  
pp. 1941-1948 ◽  
Author(s):  
Constance J. Jeffery
Keyword(s):  
Molecular Mechanisms ◽  
Food Crops ◽  
Bacterial Strains ◽  
Cellular Processes ◽  
Biochemical Pathways ◽  
The Past ◽  
Single Polypeptide Chain ◽  
New Antibiotics ◽  
Moonlighting Proteins ◽  
Single Polypeptide

During the past few decades, it's become clear that many enzymes evolved not only to act as specific, finely tuned and carefully regulated catalysts, but also to perform a second, completely different function in the cell. In general, these moonlighting proteins have a single polypeptide chain that performs two or more distinct and physiologically relevant biochemical or biophysical functions. This mini-review describes examples of moonlighting proteins that have been found within the past few years, including some that play key roles in human and animal diseases and in the regulation of biochemical pathways in food crops. Several belong to two of the most common subclasses of moonlighting proteins: trigger enzymes and intracellular/surface moonlighting proteins, but a few represent less often observed combinations of functions. These examples also help illustrate some of the current methods used for identifying proteins with multiple functions. In general, a greater understanding about the functions and molecular mechanisms of moonlighting proteins, their roles in the regulation of cellular processes, and their involvement in health and disease could aid in many areas including developing new antibiotics, predicting the functions of the millions of proteins being identified through genome sequencing projects, designing novel proteins, using biological circuitry analysis to construct bacterial strains that are better producers of materials for industrial use, and developing methods to tweak biochemical pathways for increasing yields of food crops.

scholarly journals Differential expression of DLG1 as a common trait in different human diseases: an encouraging issue in molecular pathology

2019 ◽  
Vol 400 (6) ◽  
pp. 699-710 ◽  
Author(s):  
Federico Marziali ◽  
María Paula Dizanzo ◽  
Ana Laura Cavatorta ◽  
Daniela Gardiol
Keyword(s):  
Posttranslational Modifications ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Gene Mutations ◽  
Scaffolding Protein ◽  
Cellular Processes ◽  
Cell Localization ◽  
Open Questions ◽  
Therapeutic Tools ◽  
And Migration

AbstractHuman disc large (DLG1) is a scaffolding protein that through the interaction with diverse cell partners participates in the control of key cellular processes such as polarity, proliferation and migration. Experimental data have mainly identified DLG1 as a tumor suppressor. An outstanding point for DLG1 protein is that altered DLG1 expression andDLG1gene mutations were observed in different pathologies, including cancer and neurological and immunological disorders. Evident changes in DLG1 abundance and/or cell localization were identified in a number of studies suggesting its participation in molecular mechanisms responsible for the development of such illnesses. In this review, we focus on some of the latest findings regarding DLG1 alterations in different diseases as well as its potential use as a biomarker for pathological progression. We further address the current knowledge on the molecular mechanisms regulating DLG1 expression and the posttranslational modifications that may affect DLG1 cell localization and functions. Despite the advances in this field, there are still open questions about the precise molecular link between alterations in DLG1 expression and the development of each specific pathology. The complete understanding of this concern will give us new scenarios for the design of promising diagnosis and therapeutic tools.

scholarly journals The Functional Role of Long Non-Coding RNAs in Melanoma

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4848
Author(s):  
Michal Wozniak ◽  
Malgorzata Czyz
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Protein Complexes ◽  
Close Association ◽  
Response To Treatment ◽  
Rna Molecules ◽  
Cellular Processes ◽  
Molecular Events ◽  
Melanoma Treatment

Melanoma is the most lethal skin cancer, with increasing incidence worldwide. The molecular events that drive melanoma development and progression have been extensively studied, resulting in significant improvements in diagnostics and therapeutic approaches. However, a high drug resistance to targeted therapies and adverse effects of immunotherapies are still a major challenge in melanoma treatment. Therefore, the elucidation of molecular mechanisms of melanomagenesis and cancer response to treatment is of great importance. Recently, many studies have revealed the close association of long noncoding RNAs (lncRNAs) with the development of many cancers, including melanoma. These RNA molecules are able to regulate a plethora of crucial cellular processes including proliferation, differentiation, migration, invasion and apoptosis through diverse mechanisms, and even slight dysregulation of their expression may lead to tumorigenesis. lncRNAs are able to bind to protein complexes, DNA and RNAs, affecting their stability, activity, and localization. They can also regulate gene expression in the nucleus. Several functions of lncRNAs are context-dependent. This review summarizes current knowledge regarding the involvement of lncRNAs in melanoma. Their possible role as prognostic markers of melanoma response to treatment and in resistance to therapy is also discussed

scholarly journals Deubiquitinase MYSM1 in the Hematopoietic System and beyond: A Current Review

2020 ◽  
Vol 21 (8) ◽  
pp. 3007 ◽  
Author(s):  
Amanda Fiore ◽  
Yue Liang ◽  
Yun Hsiao Lin ◽  
Jacky Tung ◽  
HanChen Wang ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Current Knowledge ◽  
Cell Types ◽  
Histone H2a ◽  
Hematopoietic Stem ◽  
Developmental Abnormalities ◽  
Cellular Processes ◽  
Different Cell Types

MYSM1 has emerged as an important regulator of hematopoietic stem cell function, blood cell production, immune response, and other aspects of mammalian physiology. It is a metalloprotease family protein with deubiquitinase catalytic activity, as well as SANT and SWIRM domains. MYSM1 normally localizes to the nucleus, where it can interact with chromatin and regulate gene expression, through deubiquitination of histone H2A and non-catalytic contacts with other transcriptional regulators. A cytosolic form of MYSM1 protein was also recently described and demonstrated to regulate signal transduction pathways of innate immunity, by promoting the deubiquitination of TRAF3, TRAF6, and RIP2. In this work we review the current knowledge on the molecular mechanisms of action of MYSM1 protein in transcriptional regulation, signal transduction, and potentially other cellular processes. The functions of MYSM1 in different cell types and aspects of mammalian physiology are also reviewed, highlighting the key checkpoints in hematopoiesis, immunity, and beyond regulated by MYSM1. Importantly, mutations in MYSM1 in human were recently linked to a rare hereditary disorder characterized by leukopenia, anemia, and other hematopoietic and developmental abnormalities. Our growing knowledge of MYSM1 functions and mechanisms of actions sheds important insights into its role in mammalian physiology and the etiology of the MYSM1-deficiency disorder in human.

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