scholarly journals Transglutaminase mediated asprosin oligomerization allows its tissue storage as fibers

2022 ◽  
Author(s):  
Yousef AT Morcos ◽  
Galyna Pryymachuk ◽  
Thorben Hoffmann ◽  
Steffen Luetke ◽  
Antje Gerken ◽  
...  
Keyword(s):  
Current View ◽  
Connective Tissues ◽  
Tissue Storage ◽  
Furin Cleavage ◽  
Fiber Network ◽  
Storage Mechanism ◽  
Musculoskeletal Tissues ◽  
Established Cell ◽  
Pka Pathway ◽  
G Protein Coupled

Asprosin, the C-terminal furin cleavage product of profibrillin-1, was reported to act as a hormone that circulates at nanomolar levels and is recruited to the liver where it induces G protein-coupled activation of the cAMP-PKA pathway and stimulates rapid glucose release into the circulation. Although derived from profibrillin-1, a multidomain extracellular matrix glycoprotein with a ubiquitous distribution in connective tissues, little is known about the tissue distribution of asprosin. In the current view, asprosin is mainly produced by white adipose tissue from where it is released into the blood in monomeric form. Here, by employing newly generated specific asprosin antibodies we monitored the distribution pattern of asprosin in human and murine connective tissues such as placenta, and muscle. Thereby we detected the presence of asprosin positive extracellular fibers. Further, by screening established cell lines for asprosin synthesis we found that most cells derived from musculoskeletal tissues render asprosin into an oligomerized form. This oligomerization is facilitated by transglutaminase activity and requires an intact fibrillin fiber network for proper linear deposition. Our data suggest a new extracellular storage mechanism of asprosin in oligomerized form which may regulate its cellular bioavailability in tissues.

Laboratory Modules for Reinforcement of Concepts Taught in Undergraduate Tissue Mechanics Course

2008 ◽  
Author(s):  
Ozan Akkus ◽  
Allison Sieving
Keyword(s):  
Undergraduate Curriculum ◽  
Tissue Mechanics ◽  
Stress And Strain ◽  
Engineering Curriculum ◽  
Connective Tissues ◽  
Strength Of Materials ◽  
Musculoskeletal Tissues ◽  
State Of Stress ◽  
Wide Range ◽  
Holistic Understanding

Tissue mechanics is one of the key courses of the Biomechanics subtrack of the undergraduate curriculum. The aims of the course include: 1) To understand the concepts of stress, strain, viscoelasticity and how these concepts apply to musculoskeletal tissues. 2) The ability to infer the state of stress and strain at a given point in a biological structure under torsional, axial, bending and other types of loads. 3) To understand the anatomy of musculoskeletal tissues. Accomplishment of these aims requires a holistic understanding of statics, strength of materials and microanatomy of connective tissues. Conveying this wide range of topics in one class is a major challenge and most textbooks on this subject lack depth either in engineering or in physiology. The purpose of this abstract is to describe the benefits of the integration of theory with experimental practice for bridging the difficult topics of statics, strength of materials and tissue anatomy within the framework of undergraduate biomedical engineering curriculum.

Update of Genetic and Molecular Causes of Adrenocortical Hyperplasias Causing Cushing Syndrome

2020 ◽  
Vol 52 (08) ◽  
pp. 598-606 ◽  
Author(s):  
Annabel Berthon ◽  
Jérôme Bertherat
Keyword(s):  
Cushing Syndrome ◽  
Fumarate Hydratase ◽  
Regulatory Subunit ◽  
Acth Stimulation ◽  
Aberrant Expression ◽  
Main Pathway ◽  
Armadillo Repeat ◽  
Pka Pathway ◽  
G Protein Coupled ◽  
Adrenal Disease

AbstractBilateral hyperplasias of the adrenal cortex are rare causes of chronic endogenous hypercortisolemia also called Cushing syndrome. These hyperplasias have been classified in two categories based on the adrenal nodule size: the micronodular types include Primary Pigmented Nodular Adrenocortical Disease (PPNAD) and isolated Micronodular Adrenal Disease (iMAD) and the macronodular also named Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH). This review discusses the genetic and molecular causes of these different forms of hyperplasia that involve mutations and dysregulation of various regulators of the cAMP/protein kinase A (PKA) pathway. PKA signaling is the main pathway controlling cortisol secretion in adrenocortical cells under ACTH stimulation. Although mutations of the regulatory subunit R1α of PKA (PRKAR1A) is the main cause of familial and sporadic PPNAD, inactivation of two cAMP-binding phosphodiesterases (PDE11A and PDE8B) are associated with iMAD even if they are also found in PPNAD and PBMAH cases. Interestingly, PBMAH that is observed in multiple familial syndrome such as APC, menin, fumarate hydratase genes, has initially been associated with the aberrant expression of G-protein coupled receptors (GPCR) leading to an activation of cAMP/PKA pathway. However, more recently, the discovery of germline mutations in Armadillo repeat containing protein 5 (ARMC5) gene in 25–50% of PBMAH patients highlights its importance in the development of PBMAH. The potential relationship between ARMC5 mutations and aberrant GPCR expression is discussed as well as the potential other causes of PBMAH.

scholarly journals Functional flexibility in institutionalized sedentary older adults

2021 ◽  
Vol 23 ◽  
Author(s):  
Michelle Matos Duarte ◽  
Vicente Martínez de Haro ◽  
Ismael Sanz Arribas ◽  
Luis A. Berlanga
Keyword(s):  
Older Adults ◽  
Physical Inactivity ◽  
Aging Process ◽  
Control Period ◽  
Scratch Test ◽  
Connective Tissues ◽  
Functional Flexibility ◽  
Musculoskeletal Tissues ◽  
Physical Exercises ◽  
Before And After

Abstract The aging process leads to deterioration in physiological functions, decreasing functional capacity. Since physical exercise reduces deleterious effects, measuring physical condition is necessary in older adults. The aim of this study was to verify the evolution of the range of motion in institutionalized sedentary older adults. The sample consisted of 19 volunteers aged 65-95 years who completed the Chair Sit-and-Reach test (CSR) and the Back-Scratch test (BS) to measure flexibility of the lower and upper limbs, respectively, before and after a period of 12 weeks without intervention. The results showed significant decrease during the control period (BS, p=0.004; CSR, p=0.001). These findings confirm that physical inactivity could lead to important loss of flexibility of institutionalized individuals, indicating decline of the elastic properties of musculoskeletal tissues and of connective tissues of joints. Therefore, the participation of institutionalized older adults in properly prescribed and guided physical exercises should be continuous and regular.

scholarly journals The G Protein-coupled Receptor Gpr1 and the Gα Protein Gpa2 Act through the cAMP-Protein Kinase A Pathway to Induce Morphogenesis inCandida albicans

2005 ◽  
Vol 16 (4) ◽  
pp. 1971-1986 ◽  
Author(s):  
Mykola M. Maidan ◽  
Larissa De Rop ◽  
Joke Serneels ◽  
Simone Exler ◽  
Steffen Rupp ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
G Protein ◽  
Mitogen Activated Protein Kinase ◽  
Camp Signaling ◽  
G Protein Coupled Receptor ◽  
Gene Encoding ◽  
Pka Pathway ◽  
G Protein Coupled ◽  
Kinase A

We investigated the role in cell morphogenesis and pathogenicity of the Candida albicans GPR1 gene, encoding the G protein-coupled receptor Gpr1. Deletion of C. albicans GPR1 has only minor effects in liquid hypha-inducing media but results in strong defects in the yeast-to-hypha transition on solid hypha-inducing media. Addition of cAMP, expression of a constitutively active allele of the Gα protein Gpa2 or of the catalytic protein kinase A subunit TPK1 restores the wild-type phenotype of the CaGPR1-deleted strain. Overexpression of HST7, encoding a component of the mitogen-activated protein kinase pathway, does not suppress the defect in filamentation. These results indicate that CaGpr1 functions upstream in the cAMP–protein kinase A (PKA) pathway. We also show that, in the presence of glucose, CaGpr1 is important for amino acid-induced transition from yeast to hyphal cells. Finally, as opposed to previous reports, we show that CaGpa2 acts downstream of CaGpr1 as activator of the cAMP–PKA pathway but that deletion of neither CaGpr1 nor CaGpa2 affects glucose-induced cAMP signaling. In contrast, the latter is abolished in strains lacking CaCdc25 or CaRas1, suggesting that the CaCdc25-CaRas1 rather than the CaGpr1-CaGpa2 module mediates glucose-induced cAMP signaling in C. albicans.

scholarly journals Distribution of the large aggregating proteoglycan versican in adult human tissues.

1996 ◽  
Vol 44 (4) ◽  
pp. 303-312 ◽  
Author(s):  
B Bode-Lesniewska ◽  
M T Dours-Zimmermann ◽  
B F Odermatt ◽  
J Briner ◽  
P U Heitz ◽  
...  
Keyword(s):  
Core Protein ◽  
Splice Variants ◽  
Polyclonal Antibodies ◽  
Elastic Fiber ◽  
Basal Layer ◽  
Human Tissues ◽  
Connective Tissues ◽  
Fiber Network ◽  
Muscle Tissues ◽  
The Media

We studied the distribution of the large hyaluronan-binding proteoglycan versican (also known as PG-M) in human adult tissues using affinity-purified polyclonal antibodies that recognize the core protein of the prominent versican splice variants VO and V1. Versican was present in the loose connective tissues of various organs and was often associated with the elastic fiber network. Furthermore, it was localized in most smooth muscle tissues and in fibrous and elastic cartilage. Versican staining was also noted in the central and peripheral nervous system, in the basal layer of the epidermis, and on the luminal surface of some glandular epithelia. In blood vessels, versican was present in all three wall layers of veins and elastic arteries. In muscular arteries the immunoreactivity was normally restricted to the tunica adventitia. However, it appeared in the media and the split elastica interna of atherosclerotically transformed vessel walls. Our survey of the distribution of versican in normal human tissues now forms the basis for extended studies of potentially aberrant versican expression during pathogenic processes.

scholarly journals G Protein-coupled Receptor Gpr4 Senses Amino Acids and Activates the cAMP-PKA Pathway inCryptococcus neoformans

2006 ◽  
Vol 17 (2) ◽  
pp. 667-679 ◽  
Author(s):  
Chaoyang Xue ◽  
Yong-Sun Bahn ◽  
Gary M. Cox ◽  
Joseph Heitman
Keyword(s):  
Amino Acids ◽  
G Protein ◽  
Detection System ◽  
Pathogenic Fungi ◽  
Coincidence Detection ◽  
Receptor Internalization ◽  
Intracellular Camp ◽  
Trigger Receptor ◽  
Pka Pathway ◽  
G Protein Coupled

The Gα protein Gpa1 governs the cAMP-PKA signaling pathway and plays a central role in virulence and differentiation in the human fungal pathogen Cryptococcus neoformans, but the signals and receptors that trigger this pathway were unknown. We identified seven putative proteins that share identity with known G protein-coupled receptors (GPCRs). One protein, Gpr4, shares limited sequence identity with the Dictyostelium discoideum cAMP receptor cAR1 and the Aspergillus nidulans GPCR protein GprH and also shares structural similarity with the Saccharomyces cerevisiae receptor Gpr1. gpr4 mutants exhibited reduced capsule production and mating defects, similar to gpa1 mutants, and exogenous cAMP suppressed both gpr4 mutant phenotypes. Epistasis analysis provides further evidence that Gpr4 functions upstream of the Gα subunit Gpa1. Gpr4-Gpr4 homomeric interactions were observed in the yeast two-hybrid assay, and Gpr4 was shown to physically interact with Gpa1 in the split-ubiquitin system. A Gpr4::DsRED fusion protein was localized to the plasma membrane and methionine was found to trigger receptor internalization. The analysis of intracellular cAMP levels showed that gpr4 mutants still respond to glucose but not to certain amino acids, such as methionine. Amino acids might serve as ligands for Gpr4 and could contribute to engage the cAMP-PKA pathway. Activation of the cAMP-PKA pathway by glucose and amino acids represents a nutrient coincidence detection system shared in other pathogenic fungi.

scholarly journals A G protein-coupled receptor is required in cartilaginous and dense connective tissues to maintain spine alignment

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Zhaoyang Liu ◽  
Amro A Hussien ◽  
Yunjia Wang ◽  
Terry Heckmann ◽  
Roberto Gonzalez ◽  
...  
Keyword(s):  
G Protein ◽  
Association Studies ◽  
Genetic Regulation ◽  
Biomechanical Properties ◽  
Axial Skeleton ◽  
Intervertebral Discs ◽  
G Protein Coupled Receptor ◽  
Connective Tissues ◽  
Cartilaginous Tissues ◽  
G Protein Coupled

Adolescent idiopathic scoliosis (AIS) is the most common spine disorder affecting children worldwide, yet little is known about the pathogenesis of this disorder. Here, we demonstrate that genetic regulation of structural components of the axial skeleton, the intervertebral discs, and dense connective tissues (i.e., ligaments and tendons) are essential for the maintenance of spinal alignment. We show that the adhesion G protein-coupled receptor ADGRG6, previously implicated in human AIS association studies, is required in these tissues to maintain typical spine alignment in mice. Furthermore, we show that ADGRG6 regulates biomechanical properties of tendon and stimulates CREB signaling governing gene expression in cartilaginous tissues of the spine. Treatment with a cAMP agonist could mirror aspects of receptor function in culture, thus defining core pathways for regulating these axial cartilaginous and connective tissues. As ADGRG6 is a key gene involved in human AIS, these findings open up novel therapeutic opportunities for human scoliosis.

Spatiotemporal control of cAMP signalling processes by anchored signalling complexes

2007 ◽  
Vol 35 (5) ◽  
pp. 931-937 ◽  
Author(s):  
E. Jarnæss ◽  
K. Taskén
Keyword(s):  
Biological Effects ◽  
G Protein Coupled Receptors ◽  
Scaffolding Proteins ◽  
Extracellular Signals ◽  
Temporal Specificity ◽  
Anchoring Proteins ◽  
Induced Changes ◽  
Pka Pathway ◽  
Spatiotemporal Control ◽  
G Protein Coupled

Ligand-induced changes in cAMP concentration vary in duration, amplitude and extension into the cell. cAMP microdomains are shaped by adenylate cyclases that form cAMP as well as PDEs (phosphodiesterases) that degrade cAMP. Various extracellular signals converge on the cAMP/PKA (protein kinase A) pathway through ligand binding to GPCRs (G-protein-coupled receptors) and the cAMP/PKA pathway is therefore tightly regulated on several levels to maintain specificity in the multitude of signal inputs. AKAPs (A-kinase-anchoring proteins) target PKA to specific substrates and distinct subcellular compartments, providing spatial and temporal specificity for mediation of biological effects channelled through the cAMP/PKA pathway. AKAPs also serve as scaffolding proteins that assemble PKA together with signal terminators such as phosphoprotein phosphatases and cAMP-specific PDEs as well as components of other signalling pathways into multiprotein signalling complexes.

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