scholarly journals Lamin A/C Mechanotransduction in Laminopathies

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1306 ◽  
Author(s):  
Francesca Donnaloja ◽  
Federica Carnevali ◽  
Emanuela Jacchetti ◽  
Manuela Teresa Raimondi
Keyword(s):  
Chromatin Remodeling ◽  
Structural Integrity ◽  
Accelerated Aging ◽  
Nuclear Lamina ◽  
Cellular Processes ◽  
Skin Cells ◽  
Biological Responses ◽  
Associated Proteins ◽  
Nuclear Response ◽  
Cell Functionality

Mechanotransduction translates forces into biological responses and regulates cell functionalities. It is implicated in several diseases, including laminopathies which are pathologies associated with mutations in lamins and lamin-associated proteins. These pathologies affect muscle, adipose, bone, nerve, and skin cells and range from muscular dystrophies to accelerated aging. Although the exact mechanisms governing laminopathies and gene expression are still not clear, a strong correlation has been found between cell functionality and nuclear behavior. New theories base on the direct effect of external force on the genome, which is indeed sensitive to the force transduced by the nuclear lamina. Nuclear lamina performs two essential functions in mechanotransduction pathway modulating the nuclear stiffness and governing the chromatin remodeling. Indeed, A-type lamin mutation and deregulation has been found to affect the nuclear response, altering several downstream cellular processes such as mitosis, chromatin organization, DNA replication-transcription, and nuclear structural integrity. In this review, we summarize the recent findings on the molecular composition and architecture of the nuclear lamina, its role in healthy cells and disease regulation. We focus on A-type lamins since this protein family is the most involved in mechanotransduction and laminopathies.

scholarly journals Deciphering Nuclear Mechanobiology in Laminopathy

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 231 ◽  
Author(s):  
Jungwon Hah ◽  
Dong-Hwee Kim
Keyword(s):  
Structural Integrity ◽  
Critical Role ◽  
Nuclear Lamina ◽  
Mechanical Stimuli ◽  
Cellular Mechanics ◽  
Know How ◽  
Disease Relevance ◽  
Biochemical Signals ◽  
Nuclear Response

Extracellular mechanical stimuli are translated into biochemical signals inside the cell via mechanotransduction. The nucleus plays a critical role in mechanoregulation, which encompasses mechanosensing and mechanotransduction. The nuclear lamina underlying the inner nuclear membrane not only maintains the structural integrity, but also connects the cytoskeleton to the nuclear envelope. Lamin mutations, therefore, dysregulate the nuclear response, resulting in abnormal mechanoregulations, and ultimately, disease progression. Impaired mechanoregulations even induce malfunction in nuclear positioning, cell migration, mechanosensation, as well as differentiation. To know how to overcome laminopathies, we need to understand the mechanisms of laminopathies in a mechanobiological way. Recently, emerging studies have demonstrated the varying defects from lamin mutation in cellular homeostasis within mechanical surroundings. Therefore, this review summarizes recent findings highlighting the role of lamins, the architecture of nuclear lamina, and their disease relevance in the context of nuclear mechanobiology. We will also provide an overview of the differentiation of cellular mechanics in laminopathy.

Relationships at the nuclear envelope: lamins and nuclear pore complexes in animals and plants

2010 ◽  
Vol 38 (3) ◽  
pp. 829-831 ◽  
Author(s):  
Jindriska Fiserova ◽  
Martin W. Goldberg
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Periphery ◽  
Nuclear Lamina ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Nucleocytoplasmic Trafficking ◽  
Animal Cells ◽  
Cellular Processes ◽  
Associated Proteins ◽  
Pore Complexes

The nuclear envelope comprises a distinct compartment at the nuclear periphery that provides a platform for communication between the nucleus and cytoplasm. Signal transfer can proceed by multiple means. Primarily, this is by nucleocytoplasmic trafficking facilitated by NPCs (nuclear pore complexes). Recently, it has been indicated that signals can be transmitted from the cytoskeleton to the intranuclear structures via interlinking transmembrane proteins. In animal cells, the nuclear lamina tightly underlies the inner nuclear membrane and thus represents the protein structure located at the furthest boundary of the nucleus. It enables communication between the nucleus and the cytoplasm via its interactions with chromatin-binding proteins, transmembrane and membrane-associated proteins. Of particular interest is the interaction of the nuclear lamina with NPCs. As both structures fulfil essential roles in close proximity at the nuclear periphery, their interactions have a large impact on cellular processes resulting in affects on tissue differentiation and development. The present review concentrates on the structural and functional lamina–NPC relationship in animal cells and its potential implications to plants.

scholarly journals Yeast Isw1p Forms Two Separable Complexes In Vivo

2003 ◽  
Vol 23 (1) ◽  
pp. 80-91 ◽  
Author(s):  
Jay C. Vary, ◽  
Vamsi K. Gangaraju ◽  
Jun Qin ◽  
Carolyn Church Landel ◽  
Charles Kooperberg ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Transcriptional Regulation ◽  
Chromatin Remodeling ◽  
Elevated Temperatures ◽  
Cellular Processes ◽  
Biochemical Assays ◽  
Associated Proteins ◽  
Chromatin Remodeling Complexes ◽  
Specific Activities

ABSTRACT There are several classes of ATP-dependent chromatin remodeling complexes, which modulate the structure of chromatin to regulate a variety of cellular processes. The budding yeast, Saccharomyces cerevisiae, encodes two ATPases of the ISWI class, Isw1p and Isw2p. Previously Isw1p was shown to copurify with three other proteins. Here we identify these associated proteins and show that Isw1p forms two separable complexes in vivo (designated Isw1a and Isw1b). Biochemical assays revealed that while both have equivalent nucleosome-stimulated ATPase activities, Isw1a and Isw1b differ in their abilities to bind to DNA and nucleosomal substrates, which possibly accounts for differences in specific activities in nucleosomal spacing and sliding. In vivo, the two Isw1 complexes have overlapping functions in transcriptional regulation of some genes yet distinct functions at others. In addition, these complexes show different contributions to cell growth at elevated temperatures.

scholarly journals Emerging Roles of BRD7 in Pathophysiology

2020 ◽  
Vol 21 (19) ◽  
pp. 7127
Author(s):  
Sang Won Park ◽  
Junsik M. Lee
Keyword(s):  
Cell Cycle ◽  
Transcriptional Regulation ◽  
Nasopharyngeal Carcinoma ◽  
Chromatin Remodeling ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Cellular Processes ◽  
Regulation Of Metabolism ◽  
Associated Proteins ◽  
Obesity And Cancer

Bromodomain is a conserved structural module found in many chromatin-associated proteins. Bromodomain-containing protein 7 (BRD7) is a member of the bromodomain-containing protein family, and was discovered two decades ago as a protein that is downregulated in nasopharyngeal carcinoma. Since then, BRD7 has been implicated in a variety of cellular processes, including chromatin remodeling, transcriptional regulation, and cell cycle progression. Decreased BRD7 activity underlies the pathophysiological properties of various diseases in different organs. BRD7 plays an important role in the pathogenesis of many cancers and, more recently, its roles in the regulation of metabolism and obesity have also been highlighted. Here, we review the involvement of BRD7 in a variety of pathophysiological conditions, with a focus on glucose homeostasis, obesity, and cancer.

scholarly journals Tracking the Antibody Immunome in Sporadic Colorectal Cancer by Using Antigen Self-Assembled Protein Arrays

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2718
Author(s):  
María González-González ◽  
José María Sayagués ◽  
Luis Muñoz-Bellvís ◽  
Carlos Eduardo Pedreira ◽  
Marcello L. R. de Campos ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Utility ◽  
Genetic Alterations ◽  
Western World ◽  
Sporadic Colorectal Cancer ◽  
Protein Arrays ◽  
Humoral Immune ◽  
Cellular Processes ◽  
Healthy Donors ◽  
Associated Proteins

Sporadic Colorectal Cancer (sCRC) is the third leading cause of cancer death in the Western world, and the sCRC patients presenting with synchronic metastasis have the poorest prognosis. Genetic alterations accumulated in sCRC tumor cells translate into mutated proteins and/or abnormal protein expression levels, which contribute to the development of sCRC. Then, the tumor-associated proteins (TAAs) might induce the production of auto-antibodies (aAb) via humoral immune response. Here, Nucleic Acid Programmable Protein Arrays (NAPPArray) are employed to identify aAb in plasma samples from a set of 50 sCRC patients compared to seven healthy donors. Our goal was to establish a systematic workflow based on NAPPArray to define differential aAb profiles between healthy individuals and sCRC patients as well as between non-metastatic (n = 38) and metastatic (n = 12) sCRC, in order to gain insight into the role of the humoral immune system in controlling the development and progression of sCRC. Our results showed aAb profile based on 141 TAA including TAAs associated with biological cellular processes altered in genesis and progress of sCRC (e.g., FSCN1, VTI2 and RPS28) that discriminated healthy donors vs. sCRC patients. In addition, the potential capacity of discrimination (between non-metastatic vs. metastatic sCRC) of 7 TAAs (USP5, ML4, MARCKSL1, CKMT1B, HMOX2, VTI2, TP53) have been analyzed individually in an independent cohort of sCRC patients, where two of them (VTI2 and TP53) were validated (AUC ~75%). In turn, these findings provided novel insights into the immunome of sCRC, in combination with transcriptomics profiles and protein antigenicity characterizations, wich might lead to the identification of novel sCRC biomarkers that might be of clinical utility for early diagnosis of the tumor. These results explore the immunomic analysis as potent source for biomarkers with diagnostic and prognostic value in CRC. Additional prospective studies in larger series of patients are required to confirm the clinical utility of these novel sCRC immunomic biomarkers.

scholarly journals Isolation of HDL by sequential flotation ultracentrifugation followed by size exclusion chromatography reveals size-based enrichment of HDL-associated proteins

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jack Jingyuan Zheng ◽  
Joanne K. Agus ◽  
Brian V. Hong ◽  
Xinyu Tang ◽  
Christopher H. Rhodes ◽  
...  
Keyword(s):  
Structural Integrity ◽  
Polyacrylamide Gel Electrophoresis ◽  
Cholesterol Acyltransferase ◽  
Density Lipoprotein ◽  
Size Exclusion ◽  
High Yield ◽  
Phospholipid Transfer ◽  
Exclusion Chromatography ◽  
Associated Proteins ◽  
Alpha 1 Antitrypsin

AbstractHigh-density lipoprotein (HDL) particles have multiple beneficial and cardioprotective roles, yet our understanding of their full structural and functional repertoire is limited due to challenges in separating HDL particles from contaminating plasma proteins and other lipid-carrying particles that overlap HDL in size and/or density. Here we describe a method for isolating HDL particles using a combination of sequential flotation density ultracentrifugation and fast protein liquid chromatography with a size exclusion column. Purity was visualized by polyacrylamide gel electrophoresis and verified by proteomics, while size and structural integrity were confirmed by transmission electron microscopy. This HDL isolation method can be used to isolate a high yield of purified HDL from a low starting plasma volume for functional analyses. This method also enables investigators to select their specific HDL fraction of interest: from the least inclusive but highest purity HDL fraction eluting in the middle of the HDL peak, to pooling all of the fractions to capture the breadth of HDL particles in the original plasma sample. We show that certain proteins such as lecithin cholesterol acyltransferase (LCAT), phospholipid transfer protein (PLTP), and clusterin (CLUS) are enriched in large HDL particles whereas proteins such as alpha-2HS-glycoprotein (A2HSG), alpha-1 antitrypsin (A1AT), and vitamin D binding protein (VDBP) are enriched or found exclusively in small HDL particles.

scholarly journals Nuclear lamina defects cause ATM-dependent NF- B activation and link accelerated aging to a systemic inflammatory response

2012 ◽  
Vol 26 (20) ◽  
pp. 2311-2324 ◽  
Author(s):  
F. G. Osorio ◽  
C. Barcena ◽  
C. Soria-Valles ◽  
A. J. Ramsay ◽  
F. de Carlos ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Accelerated Aging ◽  
Nuclear Lamina ◽  
Systemic Inflammatory Response

scholarly journals NAD+Metabolism in Aging and Cancer

2019 ◽  
Vol 3 (1) ◽  
pp. 105-130 ◽  
Author(s):  
Tyler G. Demarest ◽  
Mansi Babbar ◽  
Mustafa N. Okur ◽  
Xiuli Dan ◽  
Deborah L. Croteau ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Redox Homeostasis ◽  
Accelerated Aging ◽  
Cancer Therapies ◽  
Nad Metabolism ◽  
Cellular Processes ◽  
Cancer Pathogenesis ◽  
Nicotinamide Mononucleotide ◽  
Age Related

Aging is a major risk factor for many types of cancer, and the molecular mechanisms implicated in aging, progeria syndromes, and cancer pathogenesis display considerable similarities. Maintaining redox homeostasis, efficient signal transduction, and mitochondrial metabolism is essential for genome integrity and for preventing progression to cellular senescence or tumorigenesis. NAD+is a central signaling molecule involved in these and other cellular processes implicated in age-related diseases and cancer. Growing evidence implicates NAD+decline as a major feature of accelerated aging progeria syndromes and normal aging. Administration of NAD+precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) offer promising therapeutic strategies to improve health, progeria comorbidities, and cancer therapies. This review summarizes insights from the study of aging and progeria syndromes and discusses the implications and therapeutic potential of the underlying molecular mechanisms involved in aging and how they may contribute to tumorigenesis.

scholarly journals Functionally non-redundant paralogs spe-47 and spe-50 encode FB-MO associated proteins and interact with him-8

2020 ◽  
Author(s):  
Jessica N. Clark ◽  
Gaurav Prajapati ◽  
Fermina Aldaco ◽  
Thomas J. Sokolich ◽  
Steven Keung ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Chromatin Remodeling ◽  
Duplication Event ◽  
Sperm Function ◽  
C Elegans ◽  
Conserved Sequence ◽  
Long Period ◽  
Normal Sperm ◽  
Number Of Genes ◽  
Associated Proteins

AbstractThe activation of C. elegans spermatids to crawling spermatozoa is affected by a number of genes including spe-47. Here, we investigate a paralog to spe-47: spe-50, which has a highly conserved sequence and expression, but which is not functionally redundant to spe-47. Phylogenetic analysis indicates that the duplication event that produced the paralogs occurred prior to the radiation of the Caenorhabditis species included in the analysis, allowing a long period for the paralogs to diverge in function. Furthermore, we observed that knockout mutations in both genes, either alone or together, have little effect on sperm function. However, hermaphrodites harboring both knockout mutations combined with a third mutation in the him-8 gene are nearly self-sterile due to a sperm defect, even though they have numerous apparently normal sperm within their spermathecae. We suggest that the sperm in these triple mutants are defective in fusing with oocytes, and that the effect of the him-8 mutation is due to its role in chromatin remodeling.

Lipid Cell Biology: A Focus on Lipids in Cell Division

2018 ◽  
Vol 87 (1) ◽  
pp. 839-869 ◽  
Author(s):  
Elisabeth M. Storck ◽  
Cagakan Özbalci ◽  
Ulrike S. Eggert
Keyword(s):  
Mass Spectrometry ◽  
Cell Division ◽  
Cell Biology ◽  
Chemical Biology ◽  
Structural Integrity ◽  
Advanced Imaging ◽  
Functional Roles ◽  
Lipid Interactions ◽  
Cellular Processes ◽  
Alkyl Side Chains

Cells depend on hugely diverse lipidomes for many functions. The actions and structural integrity of the plasma membrane and most organelles also critically depend on membranes and their lipid components. Despite the biological importance of lipids, our understanding of lipid engagement, especially the roles of lipid hydrophobic alkyl side chains, in key cellular processes is still developing. Emerging research has begun to dissect the importance of lipids in intricate events such as cell division. This review discusses how these structurally diverse biomolecules are spatially and temporally regulated during cell division, with a focus on cytokinesis. We analyze how lipids facilitate changes in cellular morphology during division and how they participate in key signaling events. We identify which cytokinesis proteins are associated with membranes, suggesting lipid interactions. More broadly, we highlight key unaddressed questions in lipid cell biology and techniques, including mass spectrometry, advanced imaging, and chemical biology, which will help us gain insights into the functional roles of lipids.

Sign in / Sign up

Export Citation Format

Share Document