scholarly journals Chondroitin 6-Sulfation Regulates Perineuronal Net Formation by Controlling the Stability of Aggrecan

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Shinji Miyata ◽  
Hiroshi Kitagawa
Keyword(s):  
Extracellular Matrix ◽  
Chondroitin Sulfate ◽  
Neural Plasticity ◽  
Adult Brain ◽  
Chondroitin Sulfate Proteoglycans ◽  
Perineuronal Nets ◽  
Perineuronal Net ◽  
A Disintegrin And Metalloproteinase ◽  
The Stability ◽  
Thrombospondin Motif

Perineuronal nets (PNNs) are lattice-like extracellular matrix structures composed of chondroitin sulfate proteoglycans (CSPGs). The appearance of PNNs parallels the decline of neural plasticity, and disruption of PNNs reactivates neural plasticity in the adult brain. We previously reported that sulfation patterns of chondroitin sulfate (CS) chains on CSPGs influenced the formation of PNNs and neural plasticity. However, the mechanism of PNN formation regulated by CS sulfation remains unknown. Here we found that overexpression of chondroitin 6-sulfotransferase-1 (C6ST-1), which catalyzes 6-sulfation of CS chains, selectively decreased aggrecan, a major CSPG in PNNs, in the aged brain without affecting other PNN components. Both diffuse and PNN-associated aggrecans were reduced by overexpression of C6ST-1. C6ST-1 increased 6-sulfation in both the repeating disaccharide region and linkage region of CS chains. Overexpression of 6-sulfation primarily impaired accumulation of aggrecan in PNNs, whereas condensation of other PNN components was not affected. Finally, we found that increased 6-sulfation accelerated proteolysis of aggrecan by a disintegrin and metalloproteinase domain with thrombospondin motif (ADAMTS) protease. Taken together, our results indicate that sulfation patterns of CS chains on aggrecan influenced the stability of the CSPG, thereby regulating formation of PNNs and neural plasticity.

scholarly journals Semaphorin 3A Binds to the Perineuronal Nets via Chondroitin Sulfate Type E Motifs in Rodent Brains

2013 ◽  
Vol 288 (38) ◽  
pp. 27384-27395 ◽  
Author(s):  
Gunnar Dick ◽  
Chin Lik Tan ◽  
Joao Nuno Alves ◽  
Erich M. E. Ehlert ◽  
Gregory M. Miller ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Chondroitin Sulfate ◽  
Rat Brain ◽  
Core Protein ◽  
Axon Growth ◽  
Chondroitin Sulfate Proteoglycans ◽  
Perineuronal Nets ◽  
Chondroitinase Abc ◽  
Blocking Antibody ◽  
Guidance Molecule

Chondroitin sulfate (CS) and the CS-rich extracellular matrix structures called perineuronal nets (PNNs) restrict plasticity and regeneration in the CNS. Plasticity is enhanced by chondroitinase ABC treatment that removes CS from its core protein in the chondroitin sulfate proteoglycans or by preventing the formation of PNNs, suggesting that chondroitin sulfate proteoglycans in the PNNs control plasticity. Recently, we have shown that semaphorin3A (Sema3A), a repulsive axon guidance molecule, localizes to the PNNs and is removed by chondroitinase ABC treatment (Vo, T., Carulli, D., Ehlert, E. M., Kwok, J. C., Dick, G., Mecollari, V., Moloney, E. B., Neufeld, G., de Winter, F., Fawcett, J. W., and Verhaagen, J. (2013) Mol. Cell. Neurosci. 56C, 186–200). Sema3A is therefore a candidate for a PNN effector in controlling plasticity. Here, we characterize the interaction of Sema3A with CS of the PNNs. Recombinant Sema3A interacts with CS type E (CS-E), and this interaction is involved in the binding of Sema3A to rat brain-derived PNN glycosaminoglycans, as demonstrated by the use of CS-E blocking antibody GD3G7. In addition, we investigate the release of endogenous Sema3A from rat brain by biochemical and enzymatic extractions. Our results confirm the interaction of Sema3A with CS-E containing glycosaminoglycans in the dense extracellular matrix of rat brain. We also demonstrate that the combination of Sema3A and PNN GAGs is a potent inhibitor of axon growth, and this inhibition is reduced by the CS-E blocking antibody. In conclusion, Sema3A binding to CS-E in the PNNs may be a mechanism whereby PNNs restrict growth and plasticity and may represent a possible point of intervention to facilitate neuronal plasticity.

scholarly journals HDAC6 and Miro1: Another interaction causing trouble in neurons

2019 ◽  
Vol 218 (6) ◽  
pp. 1769-1770 ◽  
Author(s):  
Ludo Van Den Bosch
Keyword(s):  
Extracellular Matrix ◽  
Chondroitin Sulfate ◽  
Axonal Transport ◽  
Axonal Growth ◽  
Growth Cones ◽  
Chondroitin Sulfate Proteoglycans ◽  
Cell Biol ◽  
Myelin Associated Glycoprotein

Myelin-associated glycoprotein and chondroitin sulfate proteoglycans in the extracellular matrix can prevent regeneration of injured axons. In this issue, Kalinski et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201702187) report that inhibition of HDAC6 prevents the deacetylation of Miro1, increases mitochondrial axonal transport, and restores the size of axonal growth cones.

scholarly journals Kelainan Matriks Ekstraseluler Agrekan pada Osteoarthritis

2020 ◽  
Vol 9 (1) ◽  
pp. 67-80
Author(s):  
Umiatin Umiatin ◽  
Jeanne A Diwinata Pawitan
Keyword(s):  
Extracellular Matrix ◽  
Enzyme Activity ◽  
Molecular Mechanisms ◽  
Cartilage Damage ◽  
Type Ii Collagen ◽  
Joint Disease ◽  
Joint Cartilage ◽  
Keywords Osteoarthritis ◽  
A Disintegrin And Metalloproteinase ◽  
Thrombospondin Motif

Abstrak Osteoarthritis (OA) merupakan penyakit sendi dengan prevalensi paling tinggi yang menyebabkan nyeri kronis dan disabilitas. Berbagai faktor antara lain faktor mekanik, biokimia dan faktor enzimatik berperan dalam perkembangan OA. Perkembangan OA dicirikan oleh degradasi berlebihan pada agrekan dalam matriks ekstraseluler tulang rawan sendi. Agrekan berfungsi menyediakan fleksibilitas, viskoelastisitas dan kompresibilitas jaringan. Struktur agrekan tidak konstan sepanjang hidup, namun mengalami perubahan yang disebabkan oleh aktivitas sintesis maupun degradasi. Degradasi agrekan merupakan penanda awal kerusakan tulang rawan sendi pada OA, yang diikuti oleh kerusakan kolagen tipe II. Sejauh ini mekanisme molekulernya belum diketahui pasti, sehingga diperlukan penelitian lebih lanjut mengenai mekanisme dan penyebab kerusakan agrekan. Tulisan ini merupakan suatu kajian naratif berdasarkan artikel dari jurnal nasional dan internasional yang bertujuan untuk memberikan informasi mengenai agrekan meliputi struktur, fungsi, dan faktor-faktor yang berperan pada perubahan struktur agrekan yang menginduksi terjadinya OA. Hasil kajian menunjukkan bahwa perubahan struktur agrekan erat kaitannya dengan perubahan fungsi mekanik tulang rawan sendi. Perubahan ini terjadi terutama karena degradasi yang disebabkan oleh aktivitas enzim, dari keluarga matriks metalloprotease (MMP) dan a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS). Dari kajian ini disimpulkan bahwa degradasi agrekan karena aktivitas enzim berperan penting dalam perkembangan OA, sehingga perlu dilakukan penelitian untuk mencari inhibitor enzim MMP dan ADAMTS sebagai agen terapeutik untuk menghambat perkembangan dan progresivitas OA. Kata kunci: osteoarthritis, matriks ektraseluler, agrekan, degradasi. Abstract Osteoarthritis (OA) is a joint disease with the highest prevalence and a major cause of chronic pain and disability. Many factors such as mechanical, biochemical, and enzymatic factors are involved in OA development. The development of OA is characterized by excessive degradation of aggrecan in the extracellular matrix of articular cartilage, which functions to provide flexibility, viscoelasticity, and tissue compressibility. The structure of aggrecan is not constant throughout life but undergoes changes caused by synthesis and degradation activities. Aggrecan degradation is an early marker of joint cartilage damage in OA, followed by type II collagen damage. However, the molecular mechanisms are not completely understood, so further research is needed on the mechanisms and causes of aggrecan damage. Here we provide a narrative review based on articles from national and international journals to describe the structure, function, and factors that contribute to the degradation of aggrecan. The results of the study show that changes in the structure of aggrecan are closely related to changes in the mechanical function of joint cartilage. This change occurs mainly due to degradation caused by enzyme activity, a family of matrix metalloproteinase (MMP) and a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS). The present study concludes that aggrecan degradation caused by enzyme activity was very crucial in the development of OA, it was needed to find MMP and ADAMTS inhibitors as a therapeutic agent to prevent the development and progression of OA. Keywords: osteoarthritis, extracellular matrix, aggrecan, degradation

scholarly journals Neuron-Glia Interactions in Neural Plasticity: Contributions of Neural Extracellular Matrix and Perineuronal Nets

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Egor Dzyubenko ◽  
Christine Gottschling ◽  
Andreas Faissner
Keyword(s):  
Extracellular Matrix ◽  
Neural Plasticity ◽  
Signal Transmission ◽  
Perineuronal Nets ◽  
Molecular Scaffold ◽  
Macromolecular Assemblies ◽  
Neuropsychiatric Diseases ◽  
The Central Nervous System ◽  
And Function

Synapses are specialized structures that mediate rapid and efficient signal transmission between neurons and are surrounded by glial cells. Astrocytes develop an intimate association with synapses in the central nervous system (CNS) and contribute to the regulation of ion and neurotransmitter concentrations. Together with neurons, they shape intercellular space to provide a stable milieu for neuronal activity. Extracellular matrix (ECM) components are synthesized by both neurons and astrocytes and play an important role in the formation, maintenance, and function of synapses in the CNS. The components of the ECM have been detected near glial processes, which abut onto the CNS synaptic unit, where they are part of the specialized macromolecular assemblies, termed perineuronal nets (PNNs). PNNs have originally been discovered by Golgi and represent a molecular scaffold deposited in the interface between the astrocyte and subsets of neurons in the vicinity of the synapse. Recent reports strongly suggest that PNNs are tightly involved in the regulation of synaptic plasticity. Moreover, several studies have implicated PNNs and the neural ECM in neuropsychiatric diseases. Here, we highlight current concepts relating to neural ECM and PNNs and describe anin vitroapproach that allows for the investigation of ECM functions for synaptogenesis.

scholarly journals The Chemorepulsive Protein Semaphorin 3A and Perineuronal Net-Mediated Plasticity

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
F. de Winter ◽  
J. C. F. Kwok ◽  
J. W. Fawcett ◽  
T. T. Vo ◽  
D. Carulli ◽  
...  
Keyword(s):  
Neural Plasticity ◽  
Neuronal Plasticity ◽  
Adult Brain ◽  
Critical Periods ◽  
Inhibitory Effects ◽  
Perineuronal Net ◽  
Neuronal Populations ◽  
Biochemical Interaction ◽  
Chondroitin Sulfate E ◽  
The Brain

During postnatal development, closure of critical periods coincides with the appearance of extracellular matrix structures, called perineuronal nets (PNN), around various neuronal populations throughout the brain. The absence or presence of PNN strongly correlates with neuronal plasticity. It is not clear how PNN regulate plasticity. The repulsive axon guidance proteins Semaphorin (Sema) 3A and Sema3B are also prominently expressed in the postnatal and adult brain. In the neocortex, Sema3A accumulates in the PNN that form around parvalbumin positive inhibitory interneurons during the closure of critical periods. Sema3A interacts with high-affinity with chondroitin sulfate E, a component of PNN. The localization of Sema3A in PNN and its inhibitory effects on developing neurites are intriguing features and may clarify how PNN mediate structural neural plasticity. In the cerebellum, enhanced neuronal plasticity as a result of an enriched environment correlates with reduced Sema3A expression in PNN. Here, we first review the distribution of Sema3A and Sema3B expression in the rat brain and the biochemical interaction of Sema3A with PNN. Subsequently, we review what is known so far about functional correlates of changes in Sema3A expression in PNN. Finally, we propose a model of how Semaphorins in the PNN may influence local connectivity.

scholarly journals Transient accumulation of perisinusoidal chondroitin sulfate proteoglycans during liver regeneration and development.

1996 ◽  
Vol 44 (9) ◽  
pp. 969-980 ◽  
Author(s):  
T Yada ◽  
N Koide ◽  
K Kimata
Keyword(s):  
Extracellular Matrix ◽  
Chondroitin Sulfate ◽  
Partial Hepatectomy ◽  
Rat Liver ◽  
Core Protein ◽  
Chondroitin Sulfate Proteoglycans ◽  
Neonatal Rat ◽  
Complete Restoration ◽  
Extracellular Matrix Components ◽  
And Function

After partial hepatectomy, the liver is capable of complete restoration of normal hepatic size, architecture, and function (regeneration). To study roles of the extracellular matrix in regeneration, the temporal and spatial sequences of deposition of several components, including collagen I, III, and IV, fibronectin, laminin, heparan sulfate proteoglycan (perlecan), and chondroitin sulfate proteoglycans were characterized by light microscopic immunohistochemistry in rat liver after 70% partial hepatectomy. Consistent with previous reports, there was a brisk mitosis of hepatocytes after the partial hepatectomy. Of the extracellular matrix components studied, 1B5 epitope generated by chondroitinase ABC digestion on chondroitin sulfate proteoglycans exhibited the most dramatic changes; the epitope was detectable as early as 1.5 hr after partial hepatectomy and its immunoreactivity reached a maximum at 24 hr, then declined gradually. This transient expression of the 1B5 epitope was also detected in neonatal rat liver during development. By Western blotting, the 1B5 epitope was found on two forms of the core protein of chondroitin sulfate proteoglycans with apparent molecular masses of 163 KD and 152 KD, which were also regulated in the same temporal manner.

Interferon Gamma Binds to Extracellular Matrix Chondroitin-Sulfate Proteoglycans, Thus Enhancing Its Cellular Response

1995 ◽  
Vol 15 (9) ◽  
pp. 1456-1465 ◽  
Author(s):  
Eva Hurt Camejo ◽  
Birgitta Rosengren ◽  
Germán Camejo ◽  
Peter Sartipy ◽  
Gunnar Fager ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Chondroitin Sulfate ◽  
Interferon Gamma ◽  
Cellular Response ◽  
Chondroitin Sulfate Proteoglycans

scholarly journals Development and Structural Variety of the Chondroitin Sulfate Proteoglycans-Contained Extracellular Matrix in the Mouse Brain

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Noriko Horii-Hayashi ◽  
Takayo Sasagawa ◽  
Wataru Matsunaga ◽  
Mayumi Nishi
Keyword(s):  
Extracellular Matrix ◽  
Chondroitin Sulfate ◽  
Brain Stem ◽  
Cranial Nerves ◽  
Lectin Histochemistry ◽  
Chondroitin Sulfate Proteoglycans ◽  
Amygdaloid Nucleus ◽  
Critical Periods ◽  
Structural Variety ◽  
The Brain

Chondroitin sulfate proteoglycans (CSPGs) are major components of the extracellular matrix (ECM) in the brain. In adult mammals, CSPGs form the specialized ECM structure perineuronal nets (PNNs) that surround somata and dendrites of certain types of neurons. PNNs restrict synaptic plasticity and regulate the closure of critical periods. Although previous studies have examined the starting period of PNN formation, focusing on primary sensory cortices, there are no systematic studies at the whole brain level. Here, we examined the starting period of PNN formation in male mice ranging in age from postnatal day 3 to week 11, mainly focusing on several cortical areas, limbic structures, hypothalamus, and brain stem, using lectin histochemistry withWisteria floribundaagglutinin (WFA). Results showed that early PNN formation was observed in several reticular formations of the brain stem related to the cranial nerves and primary somatosensory cortices. In the limbic system, PNN formation in the hippocampus started earlier than that of the amygdala. Furthermore, in the medial amygdaloid nucleus and some hypothalamic regions, WFA labeling did not show typical PNN-like forms. The present study suggests spatiotemporal differences at the beginning of PNN formation and a structural variety of CSPG-contained ECM in the brain.

scholarly journals Functional characterization of chondroitin sulfate proteoglycans of brain: interactions with neurons and neural cell adhesion molecules.

1993 ◽  
Vol 120 (3) ◽  
pp. 815-824 ◽  
Author(s):  
M Grumet ◽  
A Flaccus ◽  
R U Margolis
Keyword(s):  
Cell Adhesion ◽  
Chondroitin Sulfate ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Core Protein ◽  
Functional Characterization ◽  
Adult Brain ◽  
Chondroitin Sulfate Proteoglycans ◽  
Core Proteins ◽  
Cell Adhesion And Migration

Ng-CAM and N-CAM are cell adhesion molecules (CAMs), and each CAM can bind homophilically as demonstrated by the ability of CAM-coated beads (Covaspheres) to self-aggregate. We have found that the extent of aggregation of Covaspheres coated with either Ng-CAM or N-CAM was strongly inhibited by the intact 1D1 and 3F8 chondroitin sulfate proteoglycans of rat brain, and by the core glycoproteins resulting from chondroitinase treatment of the proteoglycans. Much higher concentrations of rat chondrosarcoma chondroitin sulfate proteoglycan (aggrecan) core proteins had no significant effect in these assays. The 1D1 and 3F8 proteoglycans also inhibited binding of neurons to Ng-CAM when mixtures of these proteins were adsorbed to polystyrene dishes. Direct binding of neurons to the proteoglycan core glycoproteins from brain but not from chondrosarcoma was demonstrated using an assay in which cell-substrate contact was initiated by centrifugation, and neuronal binding to the 1D1 proteoglycans was specifically inhibited by the 1D1 monoclonal antibody. Different forms of the 1D1 proteoglycan have been identified in developing and adult brain. The early postnatal form (neurocan) was found to bind neurons more effectively than the adult proteoglycan, which represents the C-terminal half of the larger neurocan core protein. Our results therefore indicate that certain brain proteoglycans can bind to neurons, and that Ng-CAM and N-CAM may be heterophilic ligands for neurocan and the 3F8 proteoglycan. The ability of these brain proteoglycans to inhibit adhesion of cells to CAMs may be one mechanism to modulate cell adhesion and migration in the nervous system.

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