Initial characterization of anosmin-1, a putative extracellular matrix protein synthesized by definite neuronal cell populations in the central nervous system

1996 ◽  
Vol 109 (7) ◽  
pp. 1749-1757 ◽  
Author(s):  
N. Soussi-Yanicostas ◽  
J.P. Hardelin ◽  
M.M. Arroyo-Jimenez ◽  
O. Ardouin ◽  
R. Legouis ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Extracellular Matrix ◽  
Nervous System ◽  
Cell Membrane ◽  
Heparan Sulfate ◽  
Matrix Protein ◽  
Neuronal Cell ◽  
Extracellular Matrix Protein ◽  
Cell Populations

The KAL gene is responsible for the X-chromosome linked form of Kallmann's syndrome in humans. Upon transfection of CHO cells with a human KAL cDNA, the corresponding encoded protein, KALc, was produced. This protein is N-glycosylated, secreted in the cell culture medium, and is localized at the cell surface. Several lines of evidence indicate that heparan-sulfate chains of proteoglycan(s) are involved in the binding of KALc to the cell membrane. Polyclonal and monoclonal antibodies to the purified KALc were generated. They allowed us to detect and characterize the protein encoded by the KAL gene in the chicken central nervous system at late stages of embryonic development. This protein is synthesized by definite neuronal cell populations including Purkinje cells in the cerebellum, mitral cells in the olfactory bulbs and several subpopulations in the optic tectum and the striatum. The protein, with an approximate molecular mass of 100 kDa, was named anosmin-1 in reference to the deficiency of the sense of smell which characterizes the human disease. Anosmin-1 is likely to be an extracellular matrix component. Since heparin treatment of cell membrane fractions from cerebellum and tectum resulted in the release of the protein, we suggest that one or several heparan-sulfate proteoglycans are involved in the binding of anosmin-1 to the membranes in vivo.

Definition of an extracellular matrix protein in rostral portions of the human central nervous system

1988 ◽  
Vol 438 (1-2) ◽  
pp. 315-322 ◽  
Author(s):  
Wolfgang J. Rettig ◽  
Pilar Garin Chesa ◽  
H. Richard Beresford ◽  
Myron R. Melamed ◽  
Lloyd J. Old
Keyword(s):  
Central Nervous System ◽  
Extracellular Matrix ◽  
Nervous System ◽  
Matrix Protein ◽  
Extracellular Matrix Protein ◽  
Human Central Nervous System ◽  
Definition Of

scholarly journals Specific heparan sulfate modifications stabilize the synaptic organizer MADD-4/Punctin at C. elegans neuromuscular junctions

Genetics ◽  
2021 ◽  
Author(s):  
Mélissa Cizeron ◽  
Laure Granger ◽  
Hannes E BÜlow ◽  
Jean-Louis Bessereau
Keyword(s):  
Heparan Sulfate ◽  
Matrix Protein ◽  
Neuromuscular Junctions ◽  
Core Protein ◽  
Extracellular Matrix Protein ◽  
Inhibitory Synapses ◽  
Single Chain ◽  
C Elegans ◽  
Sugar Chains

Abstract Heparan sulfate proteoglycans contribute to the structural organization of various neurochemical synapses. Depending on the system, their role involves either the core protein or the glycosaminoglycan chains. These linear sugar chains are extensively modified by heparan sulfate modification enzymes, resulting in highly diverse molecules. Specific modifications of glycosaminoglycan chains may thus contribute to a sugar code involved in synapse specificity. Caenorhabditis elegans is particularly useful to address this question because of the low level of genomic redundancy of these enzymes, as opposed to mammals. Here, we systematically mutated the genes encoding heparan sulfate modification enzymes in C. elegans and analyzed their impact on excitatory and inhibitory neuromuscular junctions. Using single chain antibodies that recognize different heparan sulfate modification patterns, we show in vivo that these two heparan sulfate epitopes are carried by the SDN-1 core protein, the unique C. elegans syndecan orthologue, at neuromuscular junctions. Intriguingly, these antibodies differentially bind to excitatory and inhibitory synapses, implying unique heparan sulfate modification patterns at different neuromuscular junctions. Moreover, while most enzymes are individually dispensable for proper organization of neuromuscular junctions, we show that 3-O-sulfation of SDN-1 is required to maintain wild-type levels of the extracellular matrix protein MADD-4/Punctin, a central synaptic organizer that defines the identity of excitatory and inhibitory synaptic domains at the plasma membrane of muscle cells.

Restrictin: a chick neural extracellular matrix protein involved in cell attachment co-purifies with the cell recognition molecule F11

Development ◽  
1991 ◽  
Vol 113 (1) ◽  
pp. 151-164 ◽  
Author(s):  
F.G. Rathjen ◽  
J.M. Wolff ◽  
R. Chiquet-Ehrismann
Keyword(s):  
Extracellular Matrix ◽  
Nervous System ◽  
Matrix Protein ◽  
Cell Attachment ◽  
Extracellular Matrix Protein ◽  
Relative Molecular Mass ◽  
Adhesion Assay ◽  
Cell Recognition ◽  
Neural Extracellular Matrix ◽  
Recognition Molecule

We report here the characterization of restrictin, a novel chick neural extracellular matrix glycoprotein associated with the cell recognition molecule F11. Immunoaffinity chromatography using monoclonal antibody 23–13 directed to restrictin yield a major relative molecular mass band at 170 × 10(3) and minor bands at 160, 180, 250 and 320 × 10(3) which are immunologically related to each other. Neural cells attach on immobilized restrictin in a short-term adhesion assay. This adhesion can be blocked specifically by monoclonal or polyclonal antibodies to restrictin but not by antibodies to F11 or by the peptide GRGDSP. Antibodies to restrictin do not interfere with the fasciculation of retinal axons and the isolated restrictin does not stimulate the outgrowth of axons. In the developing nervous system, restrictin is localized in very restricted regions and is found within areas of F11 expression. The timing and pattern of expression of restrictin and its cell attachment activity suggest that it participates in developmental events of the nervous system.

Extracellular Matrix Protein Matrilin-4 Regulates HSC Stress Response

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 601-601
Author(s):  
Hannah Uckelmann ◽  
Sandra Blaszkiewicz ◽  
Marieke Essers
Keyword(s):  
Cell Cycle ◽  
Bone Marrow ◽  
Extracellular Matrix ◽  
Matrix Protein ◽  
Bone Marrow Cells ◽  
Blood System ◽  
Extracellular Matrix Protein

Abstract The life-long maintenance of the blood system is accomplished by a pool of self-renewing multipotent hematopoietic stem cells (HSCs). Adult HSCs are found in a dormant state for most of their lifetime, entering cell cycle only to maintain homeostatic blood supply. Under stress conditions such as infection or chemotherapy, the loss of mature blood cells leads to an activation of dormant HSCs to replenish the blood system. Gene expression analysis performed by our group now revealed that Matrilin-4 is highly expressed in long-term HSCs (LT-HSCs) compared to short-term HSCs or committed progenitors, suggesting a potential role of Matrilin-4 in HSC function. Matrilin-4 is a member of the von Willebrand factor A-containing family of extracellular adapter proteins, which form filamentous structures outside of cells. Using mice lacking the entire family of Matrilins (1-4) we have investigated the role of Matrilins in HSC function. Constitutive Matrilin 1-4 KO mice exhibit normal hematopoiesis with a mild reduction in bone marrow cellularity and LSK numbers. However, when Matrilin KO bone marrow cells are pushed to proliferate in competitive transplantation assays with wildtype (WT) cells, they show a striking growth advantage. In a competitive transplant setting, where bone marrow cells of Matrilin KO versus WT mice are transplanted in a 1:1 ratio, the KO cells outcompete WT cells within four weeks, reaching a 90% chimerism at 16 weeks. This competitive advantage of Matrilin KO cells is evident in the long-term stem cell level as well as progenitors and is consistent in secondary transplants. To explore this remarkable phenotype, we performed single cell transplantation experiments of LT-HSCs and observed a more rapid reconstitution of peripheral blood cell levels of KO HSCs compared to WT controls. Confirming this growth advantage, Matrilin KO LSK cells show higher colony forming and serial replating potential in vitro, which can be rescued by the addition of recombinant or overexpressed Matrilin-4. While Matrilin-4 is highly expressed in homeostatic HSCs, in vivo treatment with IFNα or other inflammatory agents, such as LPS or G-CSF result in a dramatic downregulation (25-fold) of Matrilin-4 on the transcript as well as the protein level. Moreover, Matrilin KO HSCs are more sensitive to inflammatory stress, as they show a 2-fold stronger cell cycle activation in response to IFNα in vivo. Critically, Matrilin-4 KO HSCs return to the G0 state of the cell cycle normally after stress-induced activation and transplantation, thereby preventing their exhaustion. In summary, we show that the extracellular matrix protein Matrilin-4 is a novel component of the HSC niche, regulating HSC stress response. Surprisingly, HSCs lacking this extracellular matrix protein show a higher HSC potential due to an accelerated response to stress. Our data suggest that high expression of Matrilin-4 in LT-HSCs confers a resistance to stress stimuli. In situations of acute stress such as infection or transplantation however, this protection is rapidly lost to allow HSCs to efficiently replenish the blood system. Disclosures No relevant conflicts of interest to declare.

scholarly journals The extracellular matrix protein mindin serves as an integrin ligand and is critical for inflammatory cell recruitment

Blood ◽  
2005 ◽  
Vol 106 (12) ◽  
pp. 3854-3859 ◽  
Author(s):  
Wei Jia ◽  
Hong Li ◽  
You-Wen He
Keyword(s):  
Extracellular Matrix ◽  
Matrix Protein ◽  
Inflammatory Cell ◽  
Neutrophil Migration ◽  
Extracellular Matrix Protein ◽  
Hek 293 ◽  
Cell Recruitment ◽  
Inflammatory Cell Recruitment

Leukocyte recruitment to inflammation sites depends on interactions between integrins and extracellular matrix (ECM). In this report we show that mice lacking the ECM protein mindin exhibit severely impaired recruitment of neutrophils and macrophages in 4 different inflammation models. Furthermore, neutrophils directly bind to immobilized mindin, and mindin matrix mediates neutrophil migration in vitro. The adhesion of neutrophils to mindin is blocked by anti–integrin α4, anti–integrin αM, and anti–integrin β2 antibodies. We also show that HEK-293 cells transfected with cDNA encoding these integrins exhibit enhanced binding to immobilized mindin matrix and the increased binding can be blocked by anti-integrin antibodies. Our results suggest that mindin serves as a novel ligand for integrins and mindin-integrin interactions are critical for inflammatory cell recruitment in vivo.

Protective peptides derived from novel glial proteins

2000 ◽  
Vol 28 (4) ◽  
pp. 452-455 ◽  
Author(s):  
D. E. Brenneman ◽  
C. Y. Spong ◽  
I. Gozes
Keyword(s):  
Oxidative Stress ◽  
Central Nervous System ◽  
Nervous System ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Short Peptides ◽  
Significant Efficacy ◽  
The Central Nervous System ◽  
Human Neurodegenerative Disease

In studying the mediators of VIP neurotrophism in the central nervous system, two glial proteins have been discovered. Both of these proteins contain short peptides that exhibit femtomolar potency in preventing neuronal cell death from a wide variety of neurotoxic substances. Extension of these peptides to models of oxidative stress or neurodegeneration in vivo have indicated significant efficacy in protection. These peptides, both as individual agents and in combination, have promise as possible protective agents in the treatment of human neurodegenerative disease and in pathologies involving oxidative stress.

scholarly journals Loss of the Extracellular Matrix Protein DIG-1 Causes Glial Fragmentation, Dendrite Breakage and Dendrite Extension Defects

2021 ◽  
Vol 9 (4) ◽  
pp. 42
Author(s):  
Megan K. Chong ◽  
Elizabeth R. Cebul ◽  
Karolina Mizeracka ◽  
Maxwell G. Heiman
Keyword(s):  
Extracellular Matrix ◽  
Nervous System ◽  
Young Adults ◽  
Glial Cell ◽  
Sensory Neurons ◽  
Matrix Protein ◽  
Extracellular Matrix Protein ◽  
C Elegans ◽  
Cellular Integrity ◽  
Novel Alleles

The extracellular matrix (ECM) guides and constrains the shape of the nervous system. In C. elegans, DIG-1 is a giant ECM component that is required for fasciculation of sensory dendrites during development and for maintenance of axon positions throughout life. We identified four novel alleles of dig-1 in three independent screens for mutants affecting disparate aspects of neuronal and glial morphogenesis. First, we find that disruption of DIG-1 causes fragmentation of the amphid sheath glial cell in larvae and young adults. Second, it causes severing of the BAG sensory dendrite from its terminus at the nose tip, apparently due to breakage of the dendrite as animals reach adulthood. Third, it causes embryonic defects in dendrite fasciculation in inner labial (IL2) sensory neurons, as previously reported, as well as rare defects in IL2 dendrite extension that are enhanced by loss of the apical ECM component DYF-7, suggesting that apical and basolateral ECM contribute separately to dendrite extension. Our results highlight novel roles for DIG-1 in maintaining the cellular integrity of neurons and glia, possibly by creating a barrier between structures in the nervous system.

scholarly journals Ablation of the miRNA Cluster 24 Has Profound Effects on Extracellular Matrix Protein Abundance in Cartilage

2020 ◽  
Vol 21 (11) ◽  
pp. 4112
Author(s):  
Veronika S. Georgieva ◽  
Julia Etich ◽  
Björn Bluhm ◽  
Mengjie Zhu ◽  
Christian Frie ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Matrix Protein ◽  
Immunoblot Analysis ◽  
Extracellular Matrix Protein ◽  
Mirna Cluster ◽  
Rna Molecules ◽  
Genetic Ablation ◽  
Pathway Activation ◽  
Matrix Metallopeptidase

MicroRNAs (miRNAs) regulate cartilage differentiation and contribute to the onset and progression of joint degeneration. These small RNA molecules may affect extracellular matrix organization (ECM) in cartilage, but for only a few miRNAs has this role been defined in vivo. Previously, we showed that cartilage-specific genetic ablation of the Mirc24 cluster in mice leads to impaired cartilage development due to increased RAF/MEK/ERK pathway activation. Here, we studied the expression of the cluster in cartilage by LacZ reporter gene assays and determined its role for extracellular matrix homeostasis by proteome and immunoblot analysis. The cluster is expressed in prehypertrophic/hypertrophic chondrocytes of the growth plate and we now show that the cluster is also highly expressed in articular cartilage. Cartilage-specific loss of the cluster leads to increased proteoglycan 4 and matrix metallopeptidase 13 levels and decreased aggrecan and collagen X levels in epiphyseal cartilage. Interestingly, these changes are linked to a decrease in SRY-related HMG box-containing (SOX) transcription factors 6 and 9, which regulate ECM production in chondrocytes. Our data suggests that the Mirc24 cluster is important for ECM homoeostasis and the expression of transcriptional regulators of matrix production in cartilage.

scholarly journals Venular basement membranes contain specific matrix protein low expression regions that act as exit points for emigrating neutrophils

2006 ◽  
Vol 203 (6) ◽  
pp. 1519-1532 ◽  
Author(s):  
Shijun Wang ◽  
Mathieu-Benoit Voisin ◽  
Karen Y. Larbi ◽  
John Dangerfield ◽  
Christoph Scheiermann ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Serine Proteases ◽  
Matrix Protein ◽  
Unit Area ◽  
Protein Localization ◽  
Basement Membranes ◽  
Extracellular Matrix Protein ◽  
Plausible Mechanism ◽  
Low Expression

The mechanism of leukocyte migration through venular walls in vivo is largely unknown. By using immunofluorescence staining and confocal microscopy, the present study demonstrates the existence of regions within the walls of unstimulated murine cremasteric venules where expression of key vascular basement membrane (BM) constituents, laminin 10, collagen IV, and nidogen-2 (but not perlecan) are considerably lower (<60%) than the average expression detected in the same vessel. These sites were closely associated with gaps between pericytes and were preferentially used by migrating neutrophils during their passage through cytokine-stimulated venules. Although neutrophil transmigration did not alter the number/unit area of extracellular matrix protein low expression sites, the size of these regions was enlarged and their protein content was reduced in interleukin-1β–stimulated venules. These effects were entirely dependent on the presence of neutrophils and appeared to involve neutrophil-derived serine proteases. Furthermore, evidence was obtained indicating that transmigrating neutrophils carry laminins on their cell surface in vivo. Collectively, through identification of regions of low extracellular matrix protein localization that define the preferred route for transmigrating neutrophils, we have identified a plausible mechanism by which neutrophils penetrate the vascular BM without causing a gross disruption to its intricate structure.

scholarly journals Identification and characterization of a novel extracellular matrix protein nephronectin that is associated with integrin α8β1 in the embryonic kidney

2001 ◽  
Vol 154 (2) ◽  
pp. 447-458 ◽  
Author(s):  
Ralph Brandenberger ◽  
Andrea Schmidt ◽  
James Linton ◽  
Denan Wang ◽  
Carey Backus ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Matrix Protein ◽  
Extracellular Matrix Protein ◽  
Cdna Libraries ◽  
Newborn Mouse ◽  
Metanephric Mesenchyme ◽  
Rgd Sequence ◽  
Kidney Organogenesis

The epithelial–mesenchymal interactions required for kidney organogenesis are disrupted in mice lacking the integrin α8β1. None of this integrin's known ligands, however, appears to account for this phenotype. To identify a more relevant ligand, a soluble integrin α8β1 heterodimer fused to alkaline phosphatase (AP) has been used to probe blots and cDNA libraries. In newborn mouse kidney extracts, α8β1-AP detects a novel ligand of 70–90 kD. This protein, named nephronectin, is an extracellular matrix protein with five EGF-like repeats, a mucin region containing a RGD sequence, and a COOH-terminal MAM domain. Integrin α8β1 and several additional RGD-binding integrins bind nephronectin. Nephronectin mRNA is expressed in the ureteric bud epithelium, whereas α8β1 is expressed in the metanephric mesenchyme. Nephronectin is localized in the extracellular matrix in the same distribution as the ligand detected by α8β1-AP and forms a complex with α8β1 in vivo. Thus, these results strongly suggest that nephronectin is a relevant ligand mediating α8β1 function in the kidney. Nephronectin is expressed at numerous sites outside the kidney, so it may also have wider roles in development. The approaches used here should be generally useful for characterizing the interactions of novel extracellular matrix proteins identified through genomic sequencing projects.

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