scholarly journals Rab11FIP proteins link endocytic recycling vesicles for cytoskeletal transport and tethering

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Laura M. Machesky
Keyword(s):  
Motor Activity ◽  
Cell Invasion ◽  
Small Gtpase ◽  
Biological Processes ◽  
Protein Activity ◽  
Lumen Formation ◽  
Vesicle Tethering ◽  
Health And Disease ◽  
Regulated Trafficking ◽  
Insight Into

Abstract Regulated trafficking of internalised integrins and growth factor receptors enables polarisation of morphology and motility and enables lumen formation in multicellular structures. Recycling vesicles marked with Rab11 direct internalised cargo back to the plasma membrane to affect biological processes such as polarised trafficking and cancer cell invasion. A recent study by Ji and colleagues, provides insight into how the trafficking protein Rab11FIP2 links with the actin-based motor myo5b and the small GTPase Rab11 to regulate vesicle tethering and transport along actin filaments [1]. The authors used biochemical methods to demonstrate that Rab11a binds directly to the tail of myo5b and that Rab11FIP2 also forms direct interactions with both Rab11a and myo5b tails. These proteins essentially compete for binding to similar regions and thus can regulate the association and activity of each other. Ji and colleagues further demonstrate that Rab11a activates myo5b by binding to its globular tail and relieving a head-tail autoinhibition. Due to differing affinities between Rab11 and myo5b or Rab11FIP2, they propose that Rab11FIP2 mediates the association of myo5b with cargo vesicles, while Rab11a regulates the motor activity of myo5b. The present study thus elucidates how myo5b is regulated by its interactions with Rab11a and Rab11FIP2 and proposes a model for coordination of recycling vesicle tethering and motor activity. The present study has implications for how cells control polarity and motility in health and disease and suggests how Rab11FIP proteins might control motor protein activity and engagement for transport.

scholarly journals Metabolomic Interactions: An Insight into Health and Disease

2021 ◽  
pp. 61-67
Author(s):  
Maheswara Reddy Mallu ◽  
Shaik Mohammad Anjum ◽  
Sai Sri Samyutha Katravulapalli ◽  
Sri Sai Priya Avuthu ◽  
Koteswara Reddy Gujjula ◽  
...  
Keyword(s):  
Metabolic Engineering ◽  
Human Body ◽  
Metabolic Pathways ◽  
Biological Processes ◽  
Therapeutic Treatment ◽  
The Past ◽  
Metabolic Functions ◽  
Health And Disease ◽  
Metabolic Reactions ◽  
Insight Into

Over the past decade, metabolic engineering has emerged as an active and distinct discipline characterized by its over-arching emphasis on integration. In practice, metabolic engineering is the directed improvement of cellular properties through the application of modern genetic methods. The concept of metabolic regulations deals with the varied and innumerable metabolic pathways that are present in the human body. A combination of such metabolic reactions paves the way to the proper functioning of different physiological and biological processes. Dealing with the adversities of a disease, engineering of novel metabolic pathways showcases the potential of metabolic engineering and its application in the therapeutic treatment of diseases. A proper and deeper understanding of the metabolic functions in the human body can be known from simulated yeast models. This review gives a brief understanding about the interactions between the molecular set of metabolome and its complexity.

scholarly journals The History of Gene Hunting in Hereditary Spinocerebellar Degeneration: Lessons From the Past and Future Perspectives

2021 ◽  
Vol 12 ◽  
Author(s):  
Ashraf Yahia ◽  
Giovanni Stevanin
Keyword(s):  
Precision Medicine ◽  
Correct Diagnosis ◽  
Biological Processes ◽  
Spinocerebellar Degeneration ◽  
Complex Disorders ◽  
The Past ◽  
History Of ◽  
Health And Disease ◽  
Gene Hunting ◽  
Insight Into

Hereditary spinocerebellar degeneration (SCD) encompasses an expanding list of rare diseases with a broad clinical and genetic heterogeneity, complicating their diagnosis and management in daily clinical practice. Correct diagnosis is a pillar for precision medicine, a branch of medicine that promises to flourish with the progressive improvements in studying the human genome. Discovering the genes causing novel Mendelian phenotypes contributes to precision medicine by diagnosing subsets of patients with previously undiagnosed conditions, guiding the management of these patients and their families, and enabling the discovery of more causes of Mendelian diseases. This new knowledge provides insight into the biological processes involved in health and disease, including the more common complex disorders. This review discusses the evolution of the clinical and genetic approaches used to diagnose hereditary SCD and the potential of new tools for future discoveries.

An Insight into Oligopeptide Transporter 3 (OPT3) family proteins

2020 ◽  
Vol 27 ◽  
Author(s):  
Fırat Kurt
Keyword(s):  
Stress Responses ◽  
Chelating Agent ◽  
Biological Processes ◽  
Biotic And Abiotic Stress ◽  
Oligopeptide Transporter ◽  
Binding Residues ◽  
Fe Homeostasis ◽  
Proteins Interactions ◽  
Insight Into ◽  
Selection Of

: Oligopeptide transporter 3 (OPT3) proteins are one of the subsets of OPT clade, yet little is known about these transporters. Therefore, homolog OPT3 proteins in several plant species were investigated and characterized using bioinformatical tools. Motif and co-expression analyses showed that OPT3 proteins may be involved in both biotic and abiotic stress responses as well as growth and developmental processes. AtOPT3 usually seemed to take part in Fe homeostasis whereas ZmOPT3 putatively interacted with proteins involved in various biological processes from plant defense system to stress responses. Glutathione (GSH), as a putative alternative chelating agent, was used in the AtOPT3 and ZmOPT3 docking analyses to identify their putative binding residues. The information given in this study will contribute to the understanding of OPT3 proteins’ interactions in various pathways and to the selection of potential ligands for OPT3s.

scholarly journals Plant-Derived Extracellular Vesicles: Current Findings,Challenges, and Future Applications

Membranes ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 411
Author(s):  
Nader Kameli ◽  
Anya Dragojlovic-Kerkache ◽  
Paul Savelkoul ◽  
Frank R. Stassen
Keyword(s):  
Human Health ◽  
Extracellular Vesicles ◽  
Preliminary Results ◽  
In Vivo Experiments ◽  
Health And Disease ◽  
Conducting Research ◽  
Protocol Standardization ◽  
Insight Into

In recent years, plant-derived extracellular vesicles (PDEVs) have gained the interest of many experts in fields such as microbiology and immunology, and research in this field has exponentially increased. These nano-sized particles have provided researchers with a number of interesting findings, making their application in human health and disease very promising. Both in vitro and in vivo experiments have shown that PDEVs can exhibit a multitude of effects, suggesting that these vesicles may have many potential future applications, including therapeutics and nano-delivery of compounds. While the preliminary results are promising, there are still some challenges to face, such as a lack of protocol standardization, as well as knowledge gaps that need to be filled. This review aims to discuss various aspects of PDEV knowledge, including their preliminary findings, challenges, and future uses, giving insight into the complexity of conducting research in this field.

Endothelial k-RasV12 Expression Induces Capillary Deficiency Attributable to Marked Tube Network Expansion Coupled to Reduced Pericytes and Basement Membranes

2021 ◽  
Author(s):  
Zheying Sun ◽  
Scott S. Kemp ◽  
Prisca K. Lin ◽  
Kalia N. Aguera ◽  
George E. Davis
Keyword(s):  
Protein Kinase ◽  
Basement Membrane ◽  
Arteriovenous Malformations ◽  
Network Formation ◽  
Tube Formation ◽  
Small Gtpase ◽  
Basement Membranes ◽  
Formation Mechanisms ◽  
Lumen Formation ◽  
The Impact

Objective: We sought to determine how endothelial cell (EC) expression of the activating k-Ras mutation, k-RasV12, affects their ability to form lumens and tubes and interact with pericytes during capillary assembly Approach and Results: Using defined bioassays where human ECs undergo observable tubulogenesis, sprouting behavior, pericyte recruitment to EC-lined tubes, and pericyte-induced EC basement membrane deposition, we assessed the impact of EC k-RasV12 expression on these critical processes that are necessary for proper capillary network formation. This mutation, which is frequently seen in human ECs within brain arteriovenous malformations, was found to markedly accentuate EC lumen formation mechanisms, with strongly accelerated intracellular vacuole formation, vacuole fusion, and lumen expansion and with reduced sprouting behavior, leading to excessively widened tube networks compared with control ECs. These abnormal tubes demonstrate strong reductions in pericyte recruitment and pericyte-induced EC basement membranes compared with controls, with deficiencies in fibronectin, collagen type IV, and perlecan deposition. Analyses of signaling during tube formation from these k-RasV12 ECs reveals strong enhancement of Src, Pak2 (P21 [RAC1 (Rac family small GTPase 1)] activated kinase 2), b-Raf (v-raf murine sarcoma viral oncogene homolog B1), Erk (extracellular signal–related kinase), and Akt activation and increased expression of PKCε (protein kinase C epsilon), MT1-MMP (membrane-type 1 matrix metalloproteinase), acetylated tubulin and CDCP1 (CUB domain-containing protein 1; most are known EC lumen regulators). Pharmacological blockade of MT1-MMP, Src, Pak, Raf, Mek (mitogen-activated protein kinase) kinases, Cdc42 (cell division cycle 42)/Rac1, and Notch markedly interferes with lumen and tube formation from these ECs. Conclusions: Overall, this novel work demonstrates that EC expression of k-RasV12 disrupts capillary assembly due to markedly excessive lumen formation coupled with strongly reduced pericyte recruitment and basement membrane deposition, which are critical pathogenic features predisposing the vasculature to develop arteriovenous malformations.

scholarly journals Cdc42 and formin activity control non-muscle myosin dynamics during Drosophila heart morphogenesis

2014 ◽  
Vol 206 (7) ◽  
pp. 909-922 ◽  
Author(s):  
Georg Vogler ◽  
Jiandong Liu ◽  
Timothy W. Iafe ◽  
Ede Migh ◽  
József Mihály ◽  
...  
Keyword(s):  
Cell Fate ◽  
Matrix Protein ◽  
Small Gtpase ◽  
Extracellular Matrix Protein ◽  
Specific Expression ◽  
Heart Morphogenesis ◽  
Lumen Formation ◽  
Spatiotemporal Regulation ◽  
Genetic Mechanisms ◽  
Heart Formation

During heart formation, a network of transcription factors and signaling pathways guide cardiac cell fate and differentiation, but the genetic mechanisms orchestrating heart assembly and lumen formation remain unclear. Here, we show that the small GTPase Cdc42 is essential for Drosophila melanogaster heart morphogenesis and lumen formation. Cdc42 genetically interacts with the cardiogenic transcription factor tinman; with dDAAM which belongs to the family of actin organizing formins; and with zipper, which encodes nonmuscle myosin II. Zipper is required for heart lumen formation, and its spatiotemporal activity at the prospective luminal surface is controlled by Cdc42. Heart-specific expression of activated Cdc42, or the regulatory formins dDAAM and Diaphanous caused mislocalization of Zipper and induced ectopic heart lumina, as characterized by luminal markers such as the extracellular matrix protein Slit. Placement of Slit at the lumen surface depends on Cdc42 and formin function. Thus, Cdc42 and formins play pivotal roles in heart lumen formation through the spatiotemporal regulation of the actomyosin network.

scholarly journals Hidden in plain sight: What remains to be discovered in the eukaryotic proteome?

2018 ◽  
Author(s):  
Valerie Wood ◽  
Antonia Lock ◽  
Midori A. Harris ◽  
Kim Rutherford ◽  
Jürg Bähler ◽  
...  
Keyword(s):  
Gene Ontology ◽  
Fission Yeast ◽  
Genome Sequencing ◽  
Large Scale ◽  
Biological Process ◽  
Blind Spot ◽  
Model Organisms ◽  
Biological Processes ◽  
Health And Disease

AbstractThe first decade of genome sequencing stimulated an explosion in the characterization of unknown proteins. More recently, the pace of functional discovery has slowed, leaving around 20% of the proteins even in well-studied model organisms without informative descriptions of their biological roles. Remarkably, many uncharacterized proteins are conserved from yeasts to human, suggesting that they contribute to fundamental biological processes. To fully understand biological systems in health and disease, we need to account for every part of the system. Unstudied proteins thus represent a collective blind spot that limits the progress of both basic and applied biosciences.We use a simple yet powerful metric based on Gene Ontology (GO) biological process terms to define characterized and uncharacterized proteins for human, budding yeast, and fission yeast. We then identify a set of conserved but unstudied proteins in S. pombe, and classify them based on a combination of orthogonal attributes determined by large-scale experimental and comparative methods. Finally, we explore possible reasons why these proteins remain neglected, and propose courses of action to raise their profile and thereby reap the benefits of completing the catalog of proteins’ biological roles.

scholarly journals Therapeutic Depletion of Axotomy Competent Cells in Amyotrophic Lateral Sclerosis (ALS)

2019 ◽  
Vol 2 (1) ◽  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Protein Networks ◽  
Large Protein ◽  
Anatomical Structures ◽  
Therapy Options ◽  
New Therapy ◽  
Competent Cells ◽  
Health And Disease ◽  
Insight Into ◽  
Lateral Sclerosis

The present paper addresses anatomically resolved protein networks by using the Imaging Cycler Microscopy (ICM/TIS) [1,2]. ICM is capable of resolving protein networks in intact anatomical structures at a power of combinatorial molecular resolution of 65,553k , where k is the number of co-mapped proteins, e.g. 100 proteins [1-4]. This method provides insight into the laws of the spatial communication of large protein networks in health and disease, which is essential for new therapy options in diseases.

scholarly journals Role of Biological Sex in the Cardiovascular-Gut Microbiome Axis

2022 ◽  
Vol 8 ◽  
Author(s):  
Shuangyue Li ◽  
Georgios Kararigas
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Microbial Composition ◽  
Biological Sex ◽  
Technological Advances ◽  
Host Health ◽  
Health And Disease ◽  
And Function ◽  
Insight Into

There has been a recent, unprecedented interest in the role of gut microbiota in host health and disease. Technological advances have dramatically expanded our knowledge of the gut microbiome. Increasing evidence has indicated a strong link between gut microbiota and the development of cardiovascular diseases (CVD). In the present article, we discuss the contribution of gut microbiota in the development and progression of CVD. We further discuss how the gut microbiome may differ between the sexes and how it may be influenced by sex hormones. We put forward that regulation of microbial composition and function by sex might lead to sex-biased disease susceptibility, thereby offering a mechanistic insight into sex differences in CVD. A better understanding of this could identify novel targets, ultimately contributing to the development of innovative preventive, diagnostic and therapeutic strategies for men and women.

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