scholarly journals Agrin is required for survival and function of monocytic cells

Blood ◽  
2012 ◽  
Vol 119 (23) ◽  
pp. 5502-5511 ◽  
Author(s):  
Cristina Mazzon ◽  
Achille Anselmo ◽  
Cristiana Soldani ◽  
Javier Cibella ◽  
Cristina Ploia ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Matrix Protein ◽  
Synapse Formation ◽  
Myeloid Cell ◽  
Heparan Sulfate Proteoglycans ◽  
Extracellular Matrix Protein ◽  
Monocytic Cells ◽  
Hematopoietic System ◽  
Extracellular Signal ◽  
And Function

Abstract Agrin, an extracellular matrix protein belonging to the heterogeneous family of heparan sulfate proteoglycans (HSPGs), is expressed by cells of the hematopoietic system but its role in leukocyte biology is not yet clear. Here we demonstrate that agrin has a crucial, nonredundant role in myeloid cell development and functions. We have identified lineage-specific alterations that affect maturation, survival and properties of agrin-deficient monocytic cells, and occur at stages later than stem cell precursors. Our data indicate that the cell-autonomous signals delivered by agrin are sensed by macrophages through the α-DC (DG) receptor and lead to the activation of signaling pathways resulting in rearrangements of the actin cytoskeleton during the phagocytic synapse formation and phosphorylation of extracellular signal-regulated kinases (Erk 1/2). Altogether, these data identify agrin as a novel player of innate immunity.

scholarly journals The Extracellular Matrix Protein Laminin  2 Regulates the Maturation and Function of the Blood-Brain Barrier

2014 ◽  
Vol 34 (46) ◽  
pp. 15260-15280 ◽  
Author(s):  
M. J. Menezes ◽  
F. K. McClenahan ◽  
C. V. Leiton ◽  
A. Aranmolate ◽  
X. Shan ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Blood Brain Barrier ◽  
Matrix Protein ◽  
Brain Barrier ◽  
Extracellular Matrix Protein ◽  
Blood Brain ◽  
And Function

Abnormal synapse formation in agrin-depleted hippocampal neurons

1999 ◽  
Vol 112 (24) ◽  
pp. 4729-4738 ◽  
Author(s):  
A. Ferreira
Keyword(s):  
Gaba Receptors ◽  
Hippocampal Neurons ◽  
Matrix Protein ◽  
Synapse Formation ◽  
Selective Inhibition ◽  
Extracellular Matrix Protein ◽  
Protein Levels ◽  
Central Neurons ◽  
And Function ◽  
Cultured Hippocampal Neurons

Agrin, a 200 kDa extracellular matrix protein, participates in the maturation of the postsynaptic target at the neuromuscular junction. Although agrin has also been detected in central neurons, little is known about its role in the formation of their synapses. In the present study, the pattern of expression, localization and function of agrin in developing hippocampal neurons were analyzed. The results indicate that an increase in agrin protein levels precedes synaptogenesis in cultured hippocampal neurons. This increase in agrin expression is accompanied by its extracellular deposition along the distal third of the axon. To investigate whether agrin plays a role during synapse formation, its expression in cultured hippocampal neurons was suppressed by means of antisense oligonucleotide treatment. The suppression of agrin expression results in the impairment of dendritic development and the formation of fewer synapses than in non-treated or sense-treated neurons. Moreover, this decreased synaptic density is accompanied by a selective inhibition of the clustering of GABA receptors. These results lead to the conclusion that agrin may be an important regulator of the maturation of dendrites and synaptogenesis in central neurons.

scholarly journals ApoE (Apolipoprotein E) in Brain Pericytes Regulates Endothelial Function in an Isoform-Dependent Manner by Modulating Basement Membrane Components

2020 ◽  
Vol 40 (1) ◽  
pp. 128-144 ◽  
Author(s):  
Yu Yamazaki ◽  
Mitsuru Shinohara ◽  
Akari Yamazaki ◽  
Yingxue Ren ◽  
Yan W. Asmann ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Basement Membrane ◽  
Matrix Protein ◽  
Extracellular Matrix Protein ◽  
Cell Phenotype ◽  
Dependent Manner ◽  
Barrier Formation ◽  
Brain Pericytes ◽  
Membrane Components ◽  
And Function

Objective: The ε4 allele of the APOE gene ( APOE4 ) is the strongest genetic risk factor for Alzheimer disease when compared with the common ε3 allele. Although there has been significant progress in understanding how apoE4 (apolipoprotein E4) drives amyloid pathology, its effects on amyloid-independent pathways, in particular cerebrovascular integrity and function, are less clear. Approach and Results: Here, we show that brain pericytes, the mural cells of the capillary walls, differentially modulate endothelial cell phenotype in an apoE isoform-dependent manner. Extracellular matrix protein induction, tube-like structure formation, and barrier formation were lower with endothelial cells cocultured with pericytes isolated from apoE4-targeted replacement (TR) mice compared with those from apoE3-TR mice. Importantly, aged apoE4-targeted replacement mice had decreased extracellular matrix protein expression and increased plasma protein leakages compared with apoE3-TR mice. Conclusions: ApoE4 impairs pericyte-mediated basement membrane formation, potentially contributing to the cerebrovascular effects of apoE4.

scholarly journals Exercise Training-Induced Extracellular Matrix Protein Adaptation in Locomotor Muscles: A Systematic Review

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1022
Author(s):  
Efpraxia Kritikaki ◽  
Rhiannon Asterling ◽  
Lesley Ward ◽  
Kay Padget ◽  
Esther Barreiro ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Exercise Training ◽  
Matrix Protein ◽  
Adult Population ◽  
Extracellular Matrix Protein ◽  
Muscle Fibres ◽  
Muscle Adaptation ◽  
Exercise Interventions ◽  
Locomotor Muscles ◽  
And Function

Exercise training promotes muscle adaptation and remodelling by balancing the processes of anabolism and catabolism; however, the mechanisms by which exercise delays accelerated muscle wasting are not fully understood. Intramuscular extracellular matrix (ECM) proteins are essential to tissue structure and function, as they create a responsive environment for the survival and repair of the muscle fibres. However, their role in muscle adaptation is underappreciated and underinvestigated. The PubMed, COCHRANE, Scopus and CIHNAL databases were systematically searched from inception until February 2021. The inclusion criteria were on ECM adaptation after exercise training in healthy adult population. Evidence from 21 studies on 402 participants demonstrates that exercise training induces muscle remodelling, and this is accompanied by ECM adaptation. All types of exercise interventions promoted a widespread increase in collagens, glycoproteins and proteoglycans ECM transcriptomes in younger and older participants. The ECM controlling mechanisms highlighted here were concerned with myogenic and angiogenic processes during muscle adaptation and remodelling. Further research identifying the mechanisms underlying the link between ECMs and muscle adaptation will support the discovery of novel therapeutic targets and the development of personalised exercise training medicine.

scholarly journals Regulation of Synaptic Development by Astrocyte Signaling Factors and Their Emerging Roles in Substance Abuse

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 297 ◽  
Author(s):  
Christopher D. Walker ◽  
W. Christopher Risher ◽  
Mary-Louise Risher
Keyword(s):  
Substance Abuse ◽  
Bone Morphogenetic Proteins ◽  
Matrix Protein ◽  
Synapse Formation ◽  
Axon Growth ◽  
Extracellular Matrix Protein ◽  
Protein Signaling ◽  
Synaptic Development ◽  
The Central Nervous System ◽  
And Function

Astrocytes have critical functions throughout the central nervous system (CNS) and have emerged as regulators of synaptic development and function. With their highly complex morphologies, they are able to interact with thousands of synapses via peripheral astrocytic processes (PAPs), ensheathing neuronal axons and dendrites to form the tripartite synapse. In this way, astrocytes engage in crosstalk with neurons to mediate a variety of CNS processes including the regulation of extracellular matrix protein signaling, formation and maintenance of the blood-brain barrier (BBB), axon growth and guidance, homeostasis of the synaptic microenvironment, synaptogenesis, and the promotion of synaptic diversity. In this review, we discuss several key astrocyte signaling factors (thrombospondins, netrins, apolipoproteins, neuregulins, bone morphogenetic proteins, and neuroligins) in the maintenance and regulation of synapse formation. We also explore how these astrocyte signaling factors are impacted by and contribute to substance abuse, particularly alcohol and cocaine use.

scholarly journals Mice Lacking the Extracellular Matrix Protein WARP Develop Normally but Have Compromised Peripheral Nerve Structure and Function

2009 ◽  
Vol 284 (18) ◽  
pp. 12020-12030 ◽  
Author(s):  
Justin M. Allen ◽  
Laura Zamurs ◽  
Bent Brachvogel ◽  
Ursula Schlötzer-Schrehardt ◽  
Uwe Hansen ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Peripheral Nerve ◽  
Matrix Protein ◽  
Structure And Function ◽  
Extracellular Matrix Protein ◽  
Nerve Structure ◽  
And Function

1280: Increased Susceptibility to Genitovaginal Prolapse Associated with a Polymorphism in the Promoter of the Extracellular Matrix Protein LAMC1

2007 ◽  
Vol 177 (4S) ◽  
pp. 421-422
Author(s):  
Ganka Nikolova ◽  
Christian O. Twiss ◽  
Hane Lee ◽  
Nelson Stanley ◽  
Janet Sinsheimer ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Matrix Protein ◽  
Extracellular Matrix Protein ◽  
Increased Susceptibility

scholarly journals Homogenous overexpression of the extracellular matrix protein Netrin-1 in a hollow fiber bioreactor

2021 ◽  
Author(s):  
Aniel Moya-Torres ◽  
Monika Gupta ◽  
Fabian Heide ◽  
Natalie Krahn ◽  
Scott Legare ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Hollow Fiber ◽  
Mammalian Cells ◽  
Matrix Protein ◽  
Continuous Production ◽  
Extracellular Matrix Protein ◽  
Close Monitoring ◽  
High Quality ◽  
Biolayer Interferometry ◽  
Hollow Fiber Bioreactor

Abstract The production of recombinant proteins for functional and biophysical studies, especially in the field of structural determination, still represents a challenge as high quality and quantities are needed to adequately perform experiments. This is in part solved by optimizing protein constructs and expression conditions to maximize the yields in regular flask expression systems. Still, work flow and effort can be substantial with no guarantee to obtain improvements. This study presents a combination of workflows that can be used to dramatically increase protein production and improve processing results, specifically for the extracellular matrix protein Netrin-1. This proteoglycan is an axon guidance cue which interacts with various receptors to initiate downstream signaling cascades affecting cell differentiation, proliferation, metabolism, and survival. We were able to produce large glycoprotein quantities in mammalian cells, which were engineered for protein overexpression and secretion into the media using the controlled environment provided by a hollow fiber bioreactor. Close monitoring of the internal bioreactor conditions allowed for stable production over an extended period of time. In addition to this, Netrin-1 concentrations were monitored in expression media through biolayer interferometry which allowed us to increase Netrin-1 media concentrations tenfold over our current flask systems while preserving excellent protein quality and in solution behavior. Our particular combination of genetic engineering, cell culture system, protein purification, and biophysical characterization permitted us to establish an efficient and continuous production of high-quality protein suitable for structural biology studies that can be translated to various biological systems. Key points • Hollow fiber bioreactor produces substantial yields of homogenous Netrin-1 • Biolayer interferometry allows target protein quantitation in expression media • High production yields in the bioreactor do not impair Netrin-1 proteoglycan quality Graphical abstract

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