Cell Biology: State-of-the-Art and Perspectives in the British Isles

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 33992

Special Issue Editors


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Guest Editor
Reader in Biomedical Science, Hull York Medical School, University of Hull, Hull HU6 7RX, UK
Interests: actin cytoskeleton; actin-binding proteins; Rho GTPases; cyclase-associated protein; coronin; plastin; cell motility; platelet biology; endothelial cell biology
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Guest Editor
Nuffield Division of Clinical Laboratory Science, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK
Interests: relationship between cancer cells and blood vessels
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue aims to provide a comprehensive overview of the state-of the-art of cell biology in the British Isles. We invite research papers that will consolidate our understanding in this broad area, both in eukaryotes and prokaryotes. The Special Issue will publish full research articles and comprehensive reviews. Potential topics include but are not limited to the following research areas:

Cell structure: organelles, cytoskeleton, cell membrane, nuclear envelope, capsule, cilia and flagella.

Cell physiology: cell growth, metabolism, protein synthesis and degradation,

cell cycle and cell division, DNA repair vesicle trafficking, intra- and

extracellular signalling, adhesion, redox biology, cell motility, cell aging and cell death, cell differentiation, multicellular development, stem cells.

OMICS: genomics, transcriptomics, proteomics, metabolomics, glycomics, lipidomics, interactomics, fluxomics, and biomics.

Cell techniques: cell and tissue culture, isolation and fractionation of cells,  immunocytochemistry, in situ hybridization, transfection, optogenetics, imaging (light microscopy, electron microscopy, superresolution), genetic manipulation, single-cell techniques.

Computational biology: modelling.

Cell biology of disease: genetic diseases, infectious diseases, cancer.

Dr. Francisco Rivero
Prof. Francesco Pezzella
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (10 papers)

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Research

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20 pages, 9288 KiB  
Article
Complex Transcriptional Profiles of the PPP1R12A Gene in Cells of the Circulatory System as Revealed by In Silico Analysis and Reverse Transcription PCR
by Paulo André Saldanha, Israel Olapeju Bolanle, Timothy Martin Palmer, Leonid Leonidovich Nikitenko and Francisco Rivero
Cells 2022, 11(15), 2315; https://doi.org/10.3390/cells11152315 - 27 Jul 2022
Cited by 1 | Viewed by 1646
Abstract
The myosin light chain phosphatase target subunit 1 (MYPT1), encoded by the PPP1R12A gene, is a key component of the myosin light chain phosphatase (MLCP) protein complex. MYPT1 isoforms have been described as products of the cassette-type alternative splicing of exons E13, E14, [...] Read more.
The myosin light chain phosphatase target subunit 1 (MYPT1), encoded by the PPP1R12A gene, is a key component of the myosin light chain phosphatase (MLCP) protein complex. MYPT1 isoforms have been described as products of the cassette-type alternative splicing of exons E13, E14, E22, and E24. Through in silico analysis of the publicly available EST and mRNA databases, we established that PPP1R12A contains 32 exons (6 more than the 26 previously reported), of which 29 are used in 11 protein-coding transcripts. An in silico analysis of publicly available RNAseq data combined with validation by reverse transcription (RT)-PCR allowed us to determine the relative abundance of each transcript in three cell types of the circulatory system where MYPT1 plays important roles: human umbilical vein endothelial cells (HUVEC), human saphenous vein smooth muscle cells (HSVSMC), and platelets. All three cell types express up to 10 transcripts at variable frequencies. HUVECs and HSVSMCs predominantly express the full-length variant (58.3% and 64.3%, respectively) followed by the variant skipping E13 (33.7% and 23.1%, respectively), whereas in platelets the predominant variants are those skipping E14 (51.4%) and E13 (19.9%), followed by the full-length variant (14.4%). Variants including E24 account for 5.4% of transcripts in platelets but are rare (<1%) in HUVECs and HSVSMCs. Complex transcriptional profiles were also found across organs using in silico analysis of RNAseq data from the GTEx project. Our findings provide a platform for future studies investigating the specific (patho)physiological roles of understudied MYPT1 isoforms. Full article
(This article belongs to the Special Issue Cell Biology: State-of-the-Art and Perspectives in the British Isles)
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15 pages, 3822 KiB  
Article
Preservation of Smooth Muscle Cell Integrity and Function: A Target for Limiting Abdominal Aortic Aneurysm Expansion?
by Emily R. Clark, Rebecca J. Helliwell, Marc A. Bailey, Karen E. Hemmings, Katherine I. Bridge, Kathryn J. Griffin, D. Julian A. Scott, Louise M. Jennings, Kirsten Riches-Suman and Karen E. Porter
Cells 2022, 11(6), 1043; https://doi.org/10.3390/cells11061043 - 19 Mar 2022
Viewed by 2675
Abstract
(1) Abdominal aortic aneurysm (AAA) is a silent, progressive disease with significant mortality from rupture. Whilst screening programmes are now able to detect this pathology early in its development, no therapeutic intervention has yet been identified to halt or retard aortic expansion. The [...] Read more.
(1) Abdominal aortic aneurysm (AAA) is a silent, progressive disease with significant mortality from rupture. Whilst screening programmes are now able to detect this pathology early in its development, no therapeutic intervention has yet been identified to halt or retard aortic expansion. The inability to obtain aortic tissue from humans at early stages has created a necessity for laboratory models, yet it is essential to create a timeline of events from EARLY to END stage AAA progression. (2) We used a previously validated ex vivo porcine bioreactor model pre-treated with protease enzyme to create “aneurysm” tissue. Mechanical properties, histological changes in the intact vessel wall, and phenotype/function of vascular smooth muscle cells (SMC) cultured from the same vessels were investigated. (3) The principal finding was significant hyperproliferation of SMC from EARLY stage vessels, but without obvious histological or SMC aberrancies. END stage tissue exhibited histological loss of α-smooth muscle actin and elastin; mechanical impairment; and, in SMC, multiple indications of senescence. (4) Aortic SMC may offer a therapeutic target for intervention, although detailed studies incorporating intervening time points between EARLY and END stage are required. Such investigations may reveal mechanisms of SMC dysfunction in AAA development and hence a therapeutic window during which SMC differentiation could be preserved or reinstated. Full article
(This article belongs to the Special Issue Cell Biology: State-of-the-Art and Perspectives in the British Isles)
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20 pages, 8486 KiB  
Article
Extracellular Signalling Modulates Scar/WAVE Complex Activity through Abi Phosphorylation
by Shashi Prakash Singh, Peter A. Thomason and Robert H. Insall
Cells 2021, 10(12), 3485; https://doi.org/10.3390/cells10123485 - 10 Dec 2021
Cited by 4 | Viewed by 3114
Abstract
The lamellipodia and pseudopodia of migrating cells are produced and maintained by the Scar/WAVE complex. Thus, actin-based cell migration is largely controlled through regulation of Scar/WAVE. Here, we report that the Abi subunit—but not Scar—is phosphorylated in response to extracellular signalling in Dictyostelium [...] Read more.
The lamellipodia and pseudopodia of migrating cells are produced and maintained by the Scar/WAVE complex. Thus, actin-based cell migration is largely controlled through regulation of Scar/WAVE. Here, we report that the Abi subunit—but not Scar—is phosphorylated in response to extracellular signalling in Dictyostelium cells. Like Scar, Abi is phosphorylated after the complex has been activated, implying that Abi phosphorylation modulates pseudopodia, rather than causing new ones to be made. Consistent with this, Scar complex mutants that cannot bind Rac are also not phosphorylated. Several environmental cues also affect Abi phosphorylation—cell-substrate adhesion promotes it and increased extracellular osmolarity diminishes it. Both unphosphorylatable and phosphomimetic Abi efficiently rescue the chemotaxis of Abi KO cells and pseudopodia formation, confirming that Abi phosphorylation is not required for activation or inactivation of the Scar/WAVE complex. However, pseudopodia and Scar patches in the cells with unphosphorylatable Abi protrude for longer, altering pseudopod dynamics and cell speed. Dictyostelium, in which Scar and Abi are both unphosphorylatable, can still form pseudopods, but migrate substantially faster. We conclude that extracellular signals and environmental responses modulate cell migration by tuning the behaviour of the Scar/WAVE complex after it has been activated. Full article
(This article belongs to the Special Issue Cell Biology: State-of-the-Art and Perspectives in the British Isles)
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19 pages, 3465 KiB  
Article
Culturing Keratinocytes on Biomimetic Substrates Facilitates Improved Epidermal Assembly In Vitro
by Eve Hunter-Featherstone, Natalie Young, Kathryn Chamberlain, Pablo Cubillas, Ben Hulette, Xingtao Wei, Jay P. Tiesman, Charles C. Bascom, Adam M. Benham, Martin W. Goldberg, Gabriele Saretzki and Iakowos Karakesisoglou
Cells 2021, 10(5), 1177; https://doi.org/10.3390/cells10051177 - 12 May 2021
Cited by 8 | Viewed by 4030
Abstract
Mechanotransduction is defined as the ability of cells to sense mechanical stimuli from their surroundings and translate them into biochemical signals. Epidermal keratinocytes respond to mechanical cues by altering their proliferation, migration, and differentiation. In vitro cell culture, however, utilises tissue culture plastic, [...] Read more.
Mechanotransduction is defined as the ability of cells to sense mechanical stimuli from their surroundings and translate them into biochemical signals. Epidermal keratinocytes respond to mechanical cues by altering their proliferation, migration, and differentiation. In vitro cell culture, however, utilises tissue culture plastic, which is significantly stiffer than the in vivo environment. Current epidermal models fail to consider the effects of culturing keratinocytes on plastic prior to setting up three-dimensional cultures, so the impact of this non-physiological exposure on epidermal assembly is largely overlooked. In this study, primary keratinocytes cultured on plastic were compared with those grown on 4, 8, and 50 kPa stiff biomimetic hydrogels that have similar mechanical properties to skin. Our data show that keratinocytes cultured on biomimetic hydrogels exhibited major changes in cellular architecture, cell density, nuclear biomechanics, and mechanoprotein expression, such as specific Linker of Nucleoskeleton and Cytoskeleton (LINC) complex constituents. Mechanical conditioning of keratinocytes on 50 kPa biomimetic hydrogels improved the thickness and organisation of 3D epidermal models. In summary, the current study demonstrates that the effects of extracellular mechanics on keratinocyte cell biology are significant and therefore should be harnessed in skin research to ensure the successful production of physiologically relevant skin models. Full article
(This article belongs to the Special Issue Cell Biology: State-of-the-Art and Perspectives in the British Isles)
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Review

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37 pages, 3201 KiB  
Review
Contribution of Model Organisms to Investigating the Far-Reaching Consequences of PRPP Metabolism on Human Health and Well-Being
by Eziuche A. Ugbogu, Lilian M. Schweizer and Michael Schweizer
Cells 2022, 11(12), 1909; https://doi.org/10.3390/cells11121909 - 13 Jun 2022
Cited by 4 | Viewed by 3508
Abstract
Phosphoribosyl pyrophosphate synthetase (PRS EC 2.7.6.1) is a rate-limiting enzyme that irreversibly catalyzes the formation of phosphoribosyl pyrophosphate (PRPP) from ribose-5-phosphate and adenosine triphosphate (ATP). This key metabolite is required for the synthesis of purine and pyrimidine nucleotides, the two aromatic amino acids [...] Read more.
Phosphoribosyl pyrophosphate synthetase (PRS EC 2.7.6.1) is a rate-limiting enzyme that irreversibly catalyzes the formation of phosphoribosyl pyrophosphate (PRPP) from ribose-5-phosphate and adenosine triphosphate (ATP). This key metabolite is required for the synthesis of purine and pyrimidine nucleotides, the two aromatic amino acids histidine and tryptophan, the cofactors nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+), all of which are essential for various life processes. Despite its ubiquity and essential nature across the plant and animal kingdoms, PRPP synthetase displays species-specific characteristics regarding the number of gene copies and architecture permitting interaction with other areas of cellular metabolism. The impact of mutated PRS genes in the model eukaryote Saccharomyces cerevisiae on cell signalling and metabolism may be relevant to the human neuropathies associated with PRPS mutations. Human PRPS1 and PRPS2 gene products are implicated in drug resistance associated with recurrent acute lymphoblastic leukaemia and progression of colorectal cancer and hepatocellular carcinoma. The investigation of PRPP metabolism in accepted model organisms, e.g., yeast and zebrafish, has the potential to reveal novel drug targets for treating at least some of the diseases, often characterized by overlapping symptoms, such as Arts syndrome and respiratory infections, and uncover the significance and relevance of human PRPS in disease diagnosis, management, and treatment. Full article
(This article belongs to the Special Issue Cell Biology: State-of-the-Art and Perspectives in the British Isles)
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19 pages, 1000 KiB  
Review
Nutrient-Response Pathways in Healthspan and Lifespan Regulation
by Aleksandra Dabrowska, Juhi Kumar and Charalampos Rallis
Cells 2022, 11(9), 1568; https://doi.org/10.3390/cells11091568 - 06 May 2022
Cited by 2 | Viewed by 3909
Abstract
Cellular, small invertebrate and vertebrate models are a driving force in biogerontology studies. Using various models, such as yeasts, appropriate tissue culture cells, Drosophila, the nematode Caenorhabditis elegans and the mouse, has tremendously increased our knowledge around the relationship between diet, nutrient-response signaling [...] Read more.
Cellular, small invertebrate and vertebrate models are a driving force in biogerontology studies. Using various models, such as yeasts, appropriate tissue culture cells, Drosophila, the nematode Caenorhabditis elegans and the mouse, has tremendously increased our knowledge around the relationship between diet, nutrient-response signaling pathways and lifespan regulation. In recent years, combinatorial drug treatments combined with mutagenesis, high-throughput screens, as well as multi-omics approaches, have provided unprecedented insights in cellular metabolism, development, differentiation, and aging. Scientists are, therefore, moving towards characterizing the fine architecture and cross-talks of growth and stress pathways towards identifying possible interventions that could lead to healthy aging and the amelioration of age-related diseases in humans. In this short review, we briefly examine recently uncovered knowledge around nutrient-response pathways, such as the Insulin Growth Factor (IGF) and the mechanistic Target of Rapamycin signaling pathways, as well as specific GWAS and some EWAS studies on lifespan and age-related disease that have enhanced our current understanding within the aging and biogerontology fields. We discuss what is learned from the rich and diverse generated data, as well as challenges and next frontiers in these scientific disciplines. Full article
(This article belongs to the Special Issue Cell Biology: State-of-the-Art and Perspectives in the British Isles)
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12 pages, 2107 KiB  
Review
Axon-Targeting Motifs: Mechanisms and Applications of Enhancing Axonal Localisation of Transmembrane Proteins
by Lloyd J. Steele-Nicholson and Melissa R. Andrews
Cells 2022, 11(6), 937; https://doi.org/10.3390/cells11060937 - 09 Mar 2022
Cited by 2 | Viewed by 3563
Abstract
Neuronal polarity established in developing neurons ensures proper function in the mature nervous system. As functionally distinct cellular compartments, axons and dendrites often require different subsets of proteins to maintain synaptic transmission and overall order. Although neurons in the mature CNS do not [...] Read more.
Neuronal polarity established in developing neurons ensures proper function in the mature nervous system. As functionally distinct cellular compartments, axons and dendrites often require different subsets of proteins to maintain synaptic transmission and overall order. Although neurons in the mature CNS do not regenerate throughout life, their interactions with their extracellular environment are dynamic. The axon remains an overall protected area of the neuron where only certain proteins have access throughout the lifespan of the cell. This is in comparison to the somatodendritic compartment, where although it too has a specialised subset of proteins required for its maintenance, many proteins destined for the axonal compartment must first be trafficked through the former. Recent research has shown that axonal proteins contain specific axon-targeting motifs that permit access to the axonal compartment as well as downstream targeting to the axonal membrane. These motifs target proteins to the axonal compartment by a variety of mechanisms including: promoting segregation into axon-targeted secretory vesicles, increasing interaction with axonal kinesins and enhancing somatodendritic endocytosis. In this review, we will discuss axon-targeting motifs within the context of established neuron trafficking mechanisms. We will also include examples of how these motifs have been applied to target proteins to the axonal compartment to improve both tools for the study of axon biology, and for use as potential therapeutics for axonopathies. Full article
(This article belongs to the Special Issue Cell Biology: State-of-the-Art and Perspectives in the British Isles)
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19 pages, 1432 KiB  
Review
Targeting Protein O-GlcNAcylation, a Link between Type 2 Diabetes Mellitus and Inflammatory Disease
by Israel Olapeju Bolanle and Timothy M. Palmer
Cells 2022, 11(4), 705; https://doi.org/10.3390/cells11040705 - 17 Feb 2022
Cited by 10 | Viewed by 3144
Abstract
Unresolved hyperglycaemia, a hallmark of type 2 diabetes mellitus (T2DM), is a well characterised manifestation of altered fuel homeostasis and our understanding of its role in the pathologic activation of the inflammatory system continues to grow. Metabolic disorders like T2DM trigger changes in [...] Read more.
Unresolved hyperglycaemia, a hallmark of type 2 diabetes mellitus (T2DM), is a well characterised manifestation of altered fuel homeostasis and our understanding of its role in the pathologic activation of the inflammatory system continues to grow. Metabolic disorders like T2DM trigger changes in the regulation of key cellular processes such as cell trafficking and proliferation, and manifest as chronic inflammatory disorders with severe long-term consequences. Activation of inflammatory pathways has recently emerged as a critical link between T2DM and inflammation. A substantial body of evidence has suggested that this is due in part to increased flux through the hexosamine biosynthetic pathway (HBP). The HBP, a unique nutrient-sensing metabolic pathway, produces the activated amino sugar UDP-GlcNAc which is a critical substrate for protein O-GlcNAcylation, a dynamic, reversible post-translational glycosylation of serine and threonine residues in target proteins. Protein O-GlcNAcylation impacts a range of cellular processes, including inflammation, metabolism, trafficking, and cytoskeletal organisation. As increased HBP flux culminates in increased protein O-GlcNAcylation, we propose that targeting O-GlcNAcylation may be a viable therapeutic strategy for the prevention and management of glucose-dependent pathologies with inflammatory components. Full article
(This article belongs to the Special Issue Cell Biology: State-of-the-Art and Perspectives in the British Isles)
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15 pages, 2110 KiB  
Review
Moving the Research Forward: The Best of British Biology Using the Tractable Model System Dictyostelium discoideum
by Robin S. B. Williams, Jonathan R. Chubb, Robert Insall, Jason S. King, Catherine J. Pears, Elinor Thompson and Cornelis J. Weijer
Cells 2021, 10(11), 3036; https://doi.org/10.3390/cells10113036 - 05 Nov 2021
Cited by 2 | Viewed by 3238
Abstract
The social amoeba Dictyostelium discoideum provides an excellent model for research across a broad range of disciplines within biology. The organism diverged from the plant, yeast, fungi and animal kingdoms around 1 billion years ago but retains common aspects found in these kingdoms. [...] Read more.
The social amoeba Dictyostelium discoideum provides an excellent model for research across a broad range of disciplines within biology. The organism diverged from the plant, yeast, fungi and animal kingdoms around 1 billion years ago but retains common aspects found in these kingdoms. Dictyostelium has a low level of genetic complexity and provides a range of molecular, cellular, biochemical and developmental biology experimental techniques, enabling multidisciplinary studies to be carried out in a wide range of areas, leading to research breakthroughs. Numerous laboratories within the United Kingdom employ Dictyostelium as their core research model. This review introduces Dictyostelium and then highlights research from several leading British research laboratories, covering their distinct areas of research, the benefits of using the model, and the breakthroughs that have arisen due to the use of Dictyostelium as a tractable model system. Full article
(This article belongs to the Special Issue Cell Biology: State-of-the-Art and Perspectives in the British Isles)
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12 pages, 1089 KiB  
Review
NUB1 and FAT10 Proteins as Potential Novel Biomarkers in Cancer: A Translational Perspective
by Maria Arshad, Nazefah Abdul Hamid, Mun Chiang Chan, Fuad Ismail, Geok Chin Tan, Francesco Pezzella and Ka-Liong Tan
Cells 2021, 10(9), 2176; https://doi.org/10.3390/cells10092176 - 24 Aug 2021
Cited by 6 | Viewed by 3547
Abstract
Cancer increases the global disease burden substantially, but it remains a challenge to manage it. The search for novel biomarkers is essential for risk assessment, diagnosis, prognosis, prediction of treatment response, and cancer monitoring. This paper examined NEDD8 ultimate buster-1 (NUB1) and F-adjacent [...] Read more.
Cancer increases the global disease burden substantially, but it remains a challenge to manage it. The search for novel biomarkers is essential for risk assessment, diagnosis, prognosis, prediction of treatment response, and cancer monitoring. This paper examined NEDD8 ultimate buster-1 (NUB1) and F-adjacent transcript 10 (FAT10) proteins as novel biomarkers in cancer. This literature review is based on the search of the electronic database, PubMed. NUB1 is an interferon-inducible protein that mediates apoptotic and anti-proliferative actions in cancer, while FAT10 is a ubiquitin-like modifier that promotes cancer. The upregulated expression of both NUB1 and FAT10 has been observed in various cancers. NUB1 protein binds to FAT10 non-covalently to promote FAT10 degradation. An overexpressed FAT10 stimulates nuclear factor-kappa β, activates the inflammatory pathways, and induces the proliferation of cancer. The FAT10 protein interacts with the mitotic arrest deficient 2 protein, causing chromosomal instability and breast tumourigenesis. FAT10 binds to the proliferating cell nuclear antigen protein and inhibits the DNA damage repair response. In addition, FAT10 involves epithelial–mesenchymal transition, invasion, apoptosis, and multiplication in hepatocellular carcinoma. Our knowledge about them is still limited. There is a need to further develop NUB1 and FAT10 as novel biomarkers. Full article
(This article belongs to the Special Issue Cell Biology: State-of-the-Art and Perspectives in the British Isles)
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