scholarly journals Skin Basement Membrane: The Foundation of Epidermal Integrity—BM Functions and Diverse Roles of Bridging Molecules Nidogen and Perlecan

2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Dirk Breitkreutz ◽  
Isabell Koxholt ◽  
Kathrin Thiemann ◽  
Roswitha Nischt
Keyword(s):  
Basement Membrane ◽  
De Novo ◽  
Molecular Assembly ◽  
Specific Gene ◽  
Stage Of Development ◽  
Molecular Aspects ◽  
And Function ◽  
Molecular Adaptors ◽  
Nidogen 1

The epidermis functions in skin as first defense line or barrier against environmental impacts, resting on extracellular matrix (ECM) of the dermis underneath. Both compartments are connected by the basement membrane (BM), composed of a set of distinct glycoproteins and proteoglycans. Herein we are reviewing molecular aspects of BM structure, composition, and function regarding not only (i) the dermoepidermal interface but also (ii) the resident microvasculature, primarily focusing on theper senonscaffold forming components perlecan and nidogen-1 and nidogen-2. Depletion or functional deficiencies of any BM component are lethal at some stage of development or around birth, though BM defects vary between organs and tissues. Lethality problems were overcome by developmental stage- and skin-specific gene targeting or by cell grafting and organotypic (3D) cocultures of normal or defective cells, which allows recapitulating BM formationde novo. Thus, evidence is accumulating that BM assembly and turnover rely on mechanical properties and composition of the adjacent ECM and the dynamics of molecular assembly, including further “minor” local components, nidogens largely functioning as catalysts or molecular adaptors and perlecan as bridging stabilizer. Collectively, orchestration of BM assembly, remodeling, and the role of individual players herein are determined by the developmental, tissue-specific, or functional context.

Specific ablation of the nidogen-binding site in the laminin γ1 chain interferes with kidney and lung development

Development ◽  
2002 ◽  
Vol 129 (11) ◽  
pp. 2711-2722 ◽  
Author(s):  
Michael Willem ◽  
Nicolai Miosge ◽  
Willi Halfter ◽  
Neil Smyth ◽  
Iris Jannetti ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Binding Site ◽  
Lung Development ◽  
Collagen Type Iv ◽  
Developmental Defects ◽  
Type Iv ◽  
And Function ◽  
Kidney Morphogenesis ◽  
Nidogen 1

Basement membrane assembly is of crucial importance in the development and function of tissues and during embryogenesis. Nidogen 1 was thought to be central in the assembly processes, connecting the networks formed by collagen type IV and laminins, however, targeted inactivation of nidogen 1 resulted in no obvious phenotype. We have now selectively deleted the sequence coding for the 56 amino acid nidogen-binding site, γ1III4, within the Lamc1 gene by gene targeting. Here, we show that mice homozygous for the deletion die immediately after birth, showing renal agenesis and impaired lung development. These developmental defects were attributed to locally restricted ruptures in the basement membrane of the elongating Wolffian duct and of alveolar sacculi. These data demonstrate that an interaction between two basement membrane proteins is required for early kidney morphogenesis in vivo.

scholarly journals Expanding Role of Ubiquitin in Translational Control

2020 ◽  
Vol 21 (3) ◽  
pp. 1151 ◽  
Author(s):  
Shannon E. Dougherty ◽  
Austin O. Maduka ◽  
Toshifumi Inada ◽  
Gustavo M. Silva
Keyword(s):  
Translational Control ◽  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Rna Binding ◽  
Protein Quality ◽  
Rna Binding Proteins ◽  
Ubiquitin Chain ◽  
Molecular Aspects ◽  
And Function

The eukaryotic proteome has to be precisely regulated at multiple levels of gene expression, from transcription, translation, and degradation of RNA and protein to adjust to several cellular conditions. Particularly at the translational level, regulation is controlled by a variety of RNA binding proteins, translation and associated factors, numerous enzymes, and by post-translational modifications (PTM). Ubiquitination, a prominent PTM discovered as the signal for protein degradation, has newly emerged as a modulator of protein synthesis by controlling several processes in translation. Advances in proteomics and cryo-electron microscopy have identified ubiquitin modifications of several ribosomal proteins and provided numerous insights on how this modification affects ribosome structure and function. The variety of pathways and functions of translation controlled by ubiquitin are determined by the various enzymes involved in ubiquitin conjugation and removal, by the ubiquitin chain type used, by the target sites of ubiquitination, and by the physiologic signals triggering its accumulation. Current research is now elucidating multiple ubiquitin-mediated mechanisms of translational control, including ribosome biogenesis, ribosome degradation, ribosome-associated protein quality control (RQC), and redox control of translation by ubiquitin (RTU). This review discusses the central role of ubiquitin in modulating the dynamism of the cellular proteome and explores the molecular aspects responsible for the expanding puzzle of ubiquitin signals and functions in translation.

An acellular human amnionic membrane model for in vitro culture of type ii pneumocytes: The role of the basement membrane in cell morphology and function

1984 ◽  
Vol 121 (1) ◽  
pp. 215-225 ◽  
Author(s):  
Jamson S. Lwebuga-Mukasa ◽  
Gunilla Thulin ◽  
Joseph A. Madri ◽  
Carolyn Barrett ◽  
Joseph B. Warshaw
Keyword(s):  
Basement Membrane ◽  
In Vitro Culture ◽  
Cell Morphology ◽  
Membrane Model ◽  
Type Ii ◽  
Type Ii Pneumocytes ◽  
And Function

scholarly journals To form and function: on the role of basement membrane mechanics in tissue development, homeostasis and disease

Open Biology ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 200360
Author(s):  
Nargess Khalilgharibi ◽  
Yanlan Mao
Keyword(s):  
Basement Membrane ◽  
Molecular Mechanisms ◽  
Disease Diagnosis ◽  
Membrane Mechanics ◽  
Form And Function ◽  
And Function ◽  
Tissue Form

The basement membrane (BM) is a special type of extracellular matrix that lines the basal side of epithelial and endothelial tissues. Functionally, the BM is important for providing physical and biochemical cues to the overlying cells, sculpting the tissue into its correct size and shape. In this review, we focus on recent studies that have unveiled the complex mechanical properties of the BM. We discuss how these properties can change during development, homeostasis and disease via different molecular mechanisms, and the subsequent impact on tissue form and function in a variety of organisms. We also explore how better characterization of BM mechanics can contribute to disease diagnosis and treatment, as well as development of better in silico and in vitro models that not only impact the fields of tissue engineering and regenerative medicine, but can also reduce the use of animals in research.

scholarly journals FOXL2: a central transcription factor of the ovary

2013 ◽  
Vol 52 (1) ◽  
pp. R17-R33 ◽  
Author(s):  
Adrien Georges ◽  
Aurelie Auguste ◽  
Laurianne Bessière ◽  
Anne Vanet ◽  
Anne-Laure Todeschini ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Forkhead Transcription Factor ◽  
Gene Encoding ◽  
Post Translational Modifications ◽  
Forkhead Box ◽  
Molecular Aspects ◽  
And Function ◽  
Craniofacial Defects ◽  
The Impact

Forkhead box L2 (FOXL2) is a gene encoding a forkhead transcription factor preferentially expressed in the ovary, the eyelids and the pituitary gland. Its germline mutations are responsible for the blepharophimosis ptosis epicanthus inversus syndrome, which includes eyelid and mild craniofacial defects associated with primary ovarian insufficiency. Recent studies have shown the involvement of FOXL2 in virtually all stages of ovarian development and function, as well as in granulosa cell (GC)-related pathologies. A central role of FOXL2 is the lifetime maintenance of GC identity through the repression of testis-specific genes. Recently, a highly recurrent somatic FOXL2 mutation leading to the p.C134W subtitution has been linked to the development of GC tumours in the adult, which account for up to 5% of ovarian malignancies. In this review, we summarise data on FOXL2 modulators, targets, partners and post-translational modifications. Despite the progresses made thus far, a better understanding of the impact of FOXL2 mutations and of the molecular aspects of its function is required to rationalise its implication in various pathophysiological processes.

scholarly journals The Role of the Proteasome in Platelet Function

2021 ◽  
Vol 22 (8) ◽  
pp. 3999
Author(s):  
Abed El-Hakim El-Kadiry ◽  
Yahye Merhi
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
De Novo ◽  
Functional Coupling ◽  
Platelet Activity ◽  
Vascular Integrity ◽  
Primary Hemostasis ◽  
Limited Protein ◽  
And Function

Platelets are megakaryocyte-derived acellular fragments prepped to maintain primary hemostasis and thrombosis by preserving vascular integrity. Although they lack nuclei, platelets harbor functional genomic mediators that bolster platelet activity in a signal-specific manner by performing limited de novo protein synthesis. Furthermore, despite their limited protein synthesis, platelets are equipped with multiple protein degradation mechanisms, such as the proteasome. In nucleated cells, the functions of the proteasome are well established and primarily include proteostasis among a myriad of other signaling processes. However, the role of proteasome-mediated protein degradation in platelets remains elusive. In this review article, we recapitulate the developing literature on the functions of the proteasome in platelets, discussing its emerging regulatory role in platelet viability and function and highlighting how its functional coupling with the transcription factor NF-κB constitutes a novel potential therapeutic target in atherothrombotic diseases.

scholarly journals Learning Naturalistic Temporal Structure in the Posterior Medial Network

2018 ◽  
Vol 30 (9) ◽  
pp. 1345-1365 ◽  
Author(s):  
Mariam Aly ◽  
Janice Chen ◽  
Nicholas B. Turk-Browne ◽  
Uri Hasson
Keyword(s):  
De Novo ◽  
Temporal Structure ◽  
Temporal Integration ◽  
Functional Coupling ◽  
Relative Role ◽  
Dynamics And Function ◽  
And Function ◽  
The Brain ◽  
Event Schemas

The posterior medial network is at the apex of a temporal integration hierarchy in the brain, integrating information over many seconds of viewing intact, but not scrambled, movies. This has been interpreted as an effect of temporal structure. Such structure in movies depends on preexisting event schemas, but temporal structure can also arise de novo from learning. Here, we examined the relative role of schema-consistent temporal structure and arbitrary but consistent temporal structure on the human posterior medial network. We tested whether, with repeated viewing, the network becomes engaged by scrambled movies with temporal structure. Replicating prior studies, activity in posterior medial regions was immediately locked to stimulus structure upon exposure to intact, but not scrambled, movies. However, for temporally structured scrambled movies, functional coupling within the network increased across stimulus repetitions, rising to the level of intact movies. Thus, temporal structure is a key determinant of network dynamics and function in the posterior medial network.

scholarly journals The morphogenetic role of midline mesendoderm and ectoderm in the development of the forebrain and the midbrain of the mouse embryo

Development ◽  
2000 ◽  
Vol 127 (9) ◽  
pp. 1799-1813 ◽  
Author(s):  
A. Camus ◽  
B.P. Davidson ◽  
S. Billiards ◽  
P. Khoo ◽  
J.A. Rivera-Perez ◽  
...  
Keyword(s):  
Neural Tube ◽  
Mouse Embryo ◽  
De Novo ◽  
Gene Activity ◽  
Anteroposterior Patterning ◽  
De Novo Gene ◽  
Ventral Neural Tube ◽  
And Function ◽  
The Impact

The anterior midline tissue (AML) of the late gastrula mouse embryo comprises the axial mesendoderm and the ventral neuroectoderm of the prospective forebrain, midbrain and rostral hindbrain. In this study, we have investigated the morphogenetic role of defined segments of the AML by testing their inductive and patterning activity and by assessing the impact of their ablation on the patterning of the neural tube at the early-somite-stage. Both rostral and caudal segments of the AML were found to induce neural gene activity in the host tissue; however, the de novo gene activity did not show any regional characteristic that might be correlated with the segmental origin of the AML. Removal of the rostral AML that contains the prechordal plate resulted in a truncation of the head accompanied by the loss of several forebrain markers. However, the remaining tissues reconstituted Gsc and Shh activity and expressed the ventral forebrain marker Nkx2.1. Furthermore, analysis of Gsc-deficient embryos reveals that the morphogenetic function of the rostral AML requires Gsc activity. Removal of the caudal AML led to a complete loss of midline molecular markers anterior to the 4th somite. In addition, Nkx2.1 expression was not detected in the ventral neural tube. The maintenance and function of the rostral AML therefore require inductive signals emanating from the caudal AML. Our results point to a role for AML in the refinement of the anteroposterior patterning and morphogenesis of the brain.

Regulating the level of intracellular hydrogen peroxide: the role of peroxiredoxin IV

2014 ◽  
Vol 42 (1) ◽  
pp. 42-46 ◽  
Author(s):  
Rachel E. Martin ◽  
Zhenbo Cao ◽  
Neil J. Bulleid
Keyword(s):  
Hydrogen Peroxide ◽  
De Novo ◽  
Protein Tyrosine Phosphatases ◽  
Disulfide Formation ◽  
Signalling Molecule ◽  
Protein Thiols ◽  
The Family ◽  
Rapid Removal ◽  
And Function

Hydrogen peroxide (H2O2) can act as a signalling molecule affecting the cell cycle as well as contributing towards the oxidative stress response. The primary target of this molecule is oxidation-sensitive cysteine residues in proteins such as protein tyrosine phosphatases. The cell has robust mechanisms to remove H2O2 that need to be regulated for H2O2 to react with and modify protein thiols. In particular, the family of peroxiredoxins are capable of the rapid removal of even trace amounts of this molecule. It has been suggested that the inactivation of peroxiredoxins by hyperoxidation may allow H2O2 levels to increase in cells and thereby modify critical thiol groups in proteins. We have been studying how the H2O2 produced during disulfide formation in the ER (endoplasmic reticulum) is metabolized and have shown that ER-resident peroxiredoxin IV not only can remove H2O2, but also contributes to de novo disulfide formation. In the present article, we review recent data on the structure and function of this enzyme as well as its sensitivity to hyperoxidation.

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