scholarly journals Signal Transduction across the Nuclear Envelope: Role of the LINC Complex in Bidirectional Signaling

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 124 ◽  
Author(s):  
Miki Hieda
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Nuclear Envelope ◽  
Cell Cycle Progression ◽  
Structural Integrity ◽  
Short Review ◽  
Linc Complex ◽  
Cellular Functions ◽  
Bidirectional Signaling ◽  
Extracellular Signal

The primary functions of the nuclear envelope are to isolate the nucleoplasm and its contents from the cytoplasm as well as maintain the spatial and structural integrity of the nucleus. The nuclear envelope also plays a role in the transfer of various molecules and signals to and from the nucleus. To reach the nucleus, an extracellular signal must be transmitted across three biological membranes: the plasma membrane, as well as the inner and outer nuclear membranes. While signal transduction across the plasma membrane is well characterized, signal transduction across the nuclear envelope, which is essential for cellular functions such as transcriptional regulation and cell cycle progression, remains poorly understood. As a physical entity, the nuclear envelope, which contains more than 100 proteins, functions as a binding scaffold for both the cytoskeleton and the nucleoskeleton, and acts in mechanotransduction by relaying extracellular signals to the nucleus. Recent results show that the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex, which is a conserved molecular bridge that spans the nuclear envelope and connects the nucleoskeleton and cytoskeleton, is also capable of transmitting information bidirectionally between the nucleus and the cytoplasm. This short review discusses bidirectional signal transduction across the nuclear envelope, with a particular focus on mechanotransduction.

scholarly journals The nuclear envelope and its involvement in cellular stress responses

2011 ◽  
Vol 39 (6) ◽  
pp. 1795-1798 ◽  
Author(s):  
Ashraf N. Malhas ◽  
David J. Vaux
Keyword(s):  
Transcription Factors ◽  
Nuclear Envelope ◽  
Stress Responses ◽  
Structural Integrity ◽  
Cellular Stress ◽  
Cellular Functions ◽  
Different Types ◽  
Cellular Stress Responses ◽  
Development And Differentiation ◽  
The Many

The nuclear envelope is not only important for the structural integrity of the nucleus, but also involved in a number of cellular functions. It has been shown to be important for maintaining and controlling chromatin organization, sequestering transcription factors, replication, transcription and signalling. The nuclear envelope is thus important for development and differentiation, and some of its components are essential for cell viability. Among the many functions which are emerging for the nuclear envelope is its involvement in protecting the cell against different types of cellular stress. In the present paper, we review key findings which describe the roles of nuclear envelope components in responses to common types of stress conditions.

Effect of Heparin-Derived Oligosaccharide on Vascular Smooth Muscle Cell Proliferation

2012 ◽  
Vol 46 (5) ◽  
pp. 393-400 ◽  
Author(s):  
Li Li ◽  
Wei Li ◽  
Zhong Ren ◽  
ShuYing He ◽  
GuangLin Xu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Messenger Rna ◽  
Cell Cycle Progression ◽  
Cellular Functions ◽  
Vsmc Proliferation ◽  
Extracellular Signal

In this study, the effect of heparin-derived oligosaccharide on bovine vascular smooth muscle cell (VSMC) proliferation and signal transduction mechanism was investigated. Extracellular-signal-regulated kinase (ERK) 1/2 has been implicated in the regulation of various cellular functions including proliferation, and we sought to define a functional role for ERK 1/2 in an established proliferation model in order to find a possible mechanism for inhibition of VSMC proliferation by heparin-derived oligosaccharide. The VSMC proliferation model was developed by platelet-derived growth factor (PDGF), and the level of ERK 1/2 protein and messenger RNA was determined by reverse transcriptase–polymerase chain reaction, Western blotting, and immunocytochemical methods. Flow cytometry analysis indicated that heparin-derived oligosaccharide blocked PDGF-induced cell cycle progression by arresting cells in the G0/G1 phase. The results imply that heparin-derived oligosaccharide inhibits VSMC proliferation by moderating the gene and the phosphorylation levels of ERK 1/2, eventually blocking G1/S transition, may be one of the mechanisms for inhibition of VSMC proliferation by heparin-derived oligosaccharide.

scholarly journals Quantification of the Spatial Organization of the Nuclear Lamina as a Tool for Cell Classification

2013 ◽  
Vol 2013 ◽  
pp. 1-6
Author(s):  
Christiaan H. Righolt ◽  
Diana A. Zatreanu ◽  
Vered Raz
Keyword(s):  
Nuclear Envelope ◽  
Spatial Organization ◽  
Structural Changes ◽  
Structural Integrity ◽  
Quantitative Description ◽  
Three Dimensional ◽  
Nuclear Lamina ◽  
Cellular Functions ◽  
Cell Classification ◽  
Nuclear Stability

The nuclear lamina is the structural scaffold of the nuclear envelope that plays multiple regulatory roles in chromatin organization and gene expression as well as a structural role in nuclear stability. The lamina proteins, also referred to as lamins, determine nuclear lamina organization and define the nuclear shape and the structural integrity of the cell nucleus. In addition, lamins are connected with both nuclear and cytoplasmic structures forming a dynamic cellular structure whose shape changes upon external and internal signals. When bound to the nuclear lamina, the lamins are mobile, have an impact on the nuclear envelop structure, and may induce changes in their regulatory functions. Changes in the nuclear lamina shape cause changes in cellular functions. A quantitative description of these structural changes could provide an unbiased description of changes in cellular function. In this review, we describe how changes in the nuclear lamina can be measured from three-dimensional images of lamins at the nuclear envelope, and we discuss how structural changes of the nuclear lamina can be used for cell classification.

scholarly journals Nuclear Envelope Regulation of Oncogenic Processes: Roles in Pancreatic Cancer

Epigenomes ◽  
2018 ◽  
Vol 2 (3) ◽  
pp. 15 ◽  
Author(s):  
Claudia Preston ◽  
Randolph Faustino
Keyword(s):  
Pancreatic Cancer ◽  
Nuclear Envelope ◽  
Nuclear Pore Complex ◽  
Structural Integrity ◽  
Radiation Treatment ◽  
Tumor Biology ◽  
Nuclear Lamina ◽  
Nucleocytoplasmic Transport ◽  
Nuclear Pore ◽  
Linc Complex

Pancreatic cancer is an aggressive and intractable malignancy with high mortality. This is due in part to a high resistance to chemotherapeutics and radiation treatment conferred by diverse regulatory mechanisms. Among these, constituents of the nuclear envelope play a significant role in regulating oncogenesis and pancreatic tumor biology, and this review focuses on three specific components and their roles in cancer. The LINC complex is a nuclear envelope component formed by proteins with SUN and KASH domains that interact in the periplasmic space of the nuclear envelope. These interactions functionally and structurally couple the cytoskeleton to chromatin and facilitates gene regulation informed by cytoplasmic activity. Furthermore, cancer cell invasiveness is impacted by LINC complex biology. The nuclear lamina is adjacent to the inner nuclear membrane of the nuclear envelope and can actively regulate chromatin in addition to providing structural integrity to the nucleus. A disrupted lamina can impart biophysical compromise to nuclear structure and function, as well as form dysfunctional micronuclei that may lead to genomic instability and chromothripsis. In close relationship to the nuclear lamina is the nuclear pore complex, a large megadalton structure that spans both outer and inner membranes of the nuclear envelope. The nuclear pore complex mediates bidirectional nucleocytoplasmic transport and is comprised of specialized proteins called nucleoporins that are overexpressed in many cancers and are diagnostic markers for oncogenesis. Furthermore, recent demonstration of gene regulatory functions for discrete nucleoporins independent of their nuclear trafficking function suggests that these proteins may contribute more to malignant phenotypes beyond serving as biomarkers. The nuclear envelope is thus a complex, intricate regulator of cell signaling, with roles in pancreatic tumorigenesis and general oncogenic transformation.

scholarly journals A molecular mechanism for LINC complex branching by structurally diverse SUN-KASH 6:6 assemblies

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Manickam Gurusaran ◽  
Owen Richard Davies
Keyword(s):  
Nuclear Envelope ◽  
Molecular Mechanism ◽  
Complex Network ◽  
Meiotic Chromosome ◽  
Force Distribution ◽  
The Sun ◽  
Linc Complex ◽  
Cellular Functions ◽  
Zinc Coordination ◽  
Chromosome Movements

The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex mechanically couples cytoskeletal and nuclear components across the nuclear envelope to fulfil a myriad of cellular functions, including nuclear shape and positioning, hearing, and meiotic chromosome movements. The canonical model is that 3:3 interactions between SUN and KASH proteins underlie the nucleocytoskeletal linkages provided by the LINC complex. Here, we provide crystallographic and biophysical evidence that SUN-KASH is a constitutive 6:6 complex in which two constituent 3:3 complexes interact head-to-head. A common SUN-KASH topology is achieved through structurally diverse 6:6 interaction mechanisms by distinct KASH proteins, including zinc-coordination by Nesprin-4. The SUN-KASH 6:6 interface provides a molecular mechanism for the establishment of integrative and distributive connections between 3:3 structures within a branched LINC complex network. In this model, SUN-KASH 6:6 complexes act as nodes for force distribution and integration between adjacent SUN and KASH molecules, enabling the coordinated transduction of large forces across the nuclear envelope.

Caveolae: Structure, Function, and Relationship to Disease

2018 ◽  
Vol 34 (1) ◽  
pp. 111-136 ◽  
Author(s):  
Robert G. Parton
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Structure Function ◽  
Lipid Composition ◽  
Mammalian Cells ◽  
Eukaryotic Cells ◽  
Interacting Proteins ◽  
Endocytic Vesicle ◽  
Cellular Functions

The plasma membrane of eukaryotic cells is not a simple sheet of lipids and proteins but is differentiated into subdomains with crucial functions. Caveolae, small pits in the plasma membrane, are the most abundant surface subdomains of many mammalian cells. The cellular functions of caveolae have long remained obscure, but a new molecular understanding of caveola formation has led to insights into their workings. Caveolae are formed by the coordinated action of a number of lipid-interacting proteins to produce a microdomain with a specific structure and lipid composition. Caveolae can bud from the plasma membrane to form an endocytic vesicle or can flatten into the membrane to help cells withstand mechanical stress. The role of caveolae as mechanoprotective and signal transduction elements is reviewed in the context of disease conditions associated with caveola dysfunction.

scholarly journals A molecular mechanism for LINC complex branching by structurally diverse SUN-KASH 6:6 assemblies

2020 ◽  
Author(s):  
Manickam Gurusaran ◽  
Owen R. Davies
Keyword(s):  
Nuclear Envelope ◽  
Molecular Mechanism ◽  
Meiotic Chromosome ◽  
Current Model ◽  
Force Distribution ◽  
The Sun ◽  
Linc Complex ◽  
Cellular Functions ◽  
Zinc Coordination ◽  
Chromosome Movements

SummaryThe LINC complex mechanically couples cytoskeletal and nuclear components across the nuclear envelope to fulfil a myriad of cellular functions, including nuclear shape and positioning, hearing and meiotic chromosome movements. The canonical model of the LINC complex is of individual linear nucleocytoskeletal linkages provided by 3:3 interactions between SUN and KASH proteins. Here, we provide crystallographic and biophysical evidence that SUN-KASH is a constitutive 6:6 complex in which two SUN trimers interact back-to-back. A common SUN-KASH topology is achieved through structurally diverse 6:6 interaction mechanisms by distinct KASH proteins, including zinc-coordination by Nesprin-4. The SUN-KASH 6:6 complex is incompatible with the current model of a linear LINC complex and instead suggests the formation of a branched LINC complex network. In this model, SUN-KASH 6:6 complexes act as nodes for force distribution and integration between adjacent SUN and KASH molecules, enabling the coordinated transduction of large forces across the nuclear envelope.

scholarly journals Keeping the LINC: the importance of nucleocytoskeletal coupling in intracellular force transmission and cellular function

2011 ◽  
Vol 39 (6) ◽  
pp. 1729-1734 ◽  
Author(s):  
Maria L. Lombardi ◽  
Jan Lammerding
Keyword(s):  
Nuclear Envelope ◽  
Complex Function ◽  
Cell Polarization ◽  
Mechanical Stimuli ◽  
Linc Complex ◽  
Force Transmission ◽  
Cellular Functions ◽  
Nuclear Lamins ◽  
Wide Range ◽  
Filament Networks

Providing a stable physical connection between the nucleus and the cytoskeleton is essential for a wide range of cellular functions and it could also participate in mechanosensing by transmitting intra- and extra-cellular mechanical stimuli via the cytoskeleton to the nucleus. Nesprins and SUN proteins, located at the nuclear envelope, form the LINC (linker of nucleoskeleton and cytoskeleton) complex that connects the nucleus to the cytoskeleton; underlying nuclear lamins contribute to anchoring LINC complex components at the nuclear envelope. Disruption of the LINC complex or loss of lamins can result in disturbed perinuclear actin and intermediate filament networks and causes severe functional defects, including impaired nuclear positioning, cell polarization and cell motility. Recent studies have identified the LINC complex as the major force-transmitting element at the nuclear envelope and suggest that many of the aforementioned defects can be attributed to disturbed force transmission between the nucleus and the cytoskeleton. Thus mutations in nesprins, SUN proteins or lamins, which have been linked to muscular dystrophies and cardiomyopathies, may weaken or completely eliminate LINC complex function at the nuclear envelope and result in impaired intracellular force transmission, thereby disrupting critical cellular functions.

Signal-regulated oxidation of proteins via MICAL

2020 ◽  
Vol 48 (2) ◽  
pp. 613-620
Author(s):  
Clara Ortegón Salas ◽  
Katharina Schneider ◽  
Christopher Horst Lillig ◽  
Manuela Gellert
Keyword(s):  
Signal Transduction ◽  
Hydrogen Peroxide ◽  
Cell Death ◽  
Redox Regulation ◽  
Signal Transduction Pathways ◽  
Cellular Functions ◽  
Intracellular Signals ◽  
Amino Acid Side Chains ◽  
Specific Receptors ◽  
Sulfur Containing

Processing of and responding to various signals is an essential cellular function that influences survival, homeostasis, development, and cell death. Extra- or intracellular signals are perceived via specific receptors and transduced in a particular signalling pathway that results in a precise response. Reversible post-translational redox modifications of cysteinyl and methionyl residues have been characterised in countless signal transduction pathways. Due to the low reactivity of most sulfur-containing amino acid side chains with hydrogen peroxide, for instance, and also to ensure specificity, redox signalling requires catalysis, just like phosphorylation signalling requires kinases and phosphatases. While reducing enzymes of both cysteinyl- and methionyl-derivates have been characterised in great detail before, the discovery and characterisation of MICAL proteins evinced the first examples of specific oxidases in signal transduction. This article provides an overview of the functions of MICAL proteins in the redox regulation of cellular functions.

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