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 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 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 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 Deacetylation of Miro1 by HDAC6 blocks mitochondrial transport and mediates axon growth inhibition

2019 ◽  
Vol 218 (6) ◽  
pp. 1871-1890 ◽  
Author(s):  
Ashley L. Kalinski ◽  
Amar N. Kar ◽  
John Craver ◽  
Andrew P. Tosolini ◽  
James N. Sleigh ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Chondroitin Sulfate ◽  
Histone Deacetylase ◽  
Growth Failure ◽  
Axon Growth ◽  
Chondroitin Sulfate Proteoglycans ◽  
Histone Deacetylase 6 ◽  
Axon Transport ◽  
Mitochondrial Transport ◽  
Myelin Associated Glycoprotein

Inhibition of histone deacetylase 6 (HDAC6) was shown to support axon growth on the nonpermissive substrates myelin-associated glycoprotein (MAG) and chondroitin sulfate proteoglycans (CSPGs). Though HDAC6 deacetylates α-tubulin, we find that another HDAC6 substrate contributes to this axon growth failure. HDAC6 is known to impact transport of mitochondria, and we show that mitochondria accumulate in distal axons after HDAC6 inhibition. Miro and Milton proteins link mitochondria to motor proteins for axon transport. Exposing neurons to MAG and CSPGs decreases acetylation of Miro1 on Lysine 105 (K105) and decreases axonal mitochondrial transport. HDAC6 inhibition increases acetylated Miro1 in axons, and acetyl-mimetic Miro1 K105Q prevents CSPG-dependent decreases in mitochondrial transport and axon growth. MAG- and CSPG-dependent deacetylation of Miro1 requires RhoA/ROCK activation and downstream intracellular Ca2+ increase, and Miro1 K105Q prevents the decrease in axonal mitochondria seen with activated RhoA and elevated Ca2+. These data point to HDAC6-dependent deacetylation of Miro1 as a mediator of axon growth inhibition through decreased mitochondrial transport.

scholarly journals Extracellular matrix in regenerating rat sciatic nerve: a comparative study on the localization of laminin, hyaluronic acid, and chondroitin sulfate proteoglycans, including versican.

1993 ◽  
Vol 41 (4) ◽  
pp. 593-599 ◽  
Author(s):  
A Tona ◽  
G Perides ◽  
F Rahemtulla ◽  
D Dahl
Keyword(s):  
Extracellular Matrix ◽  
Sciatic Nerve ◽  
Chondroitin Sulfate ◽  
Schwann Cells ◽  
Wallerian Degeneration ◽  
Polyclonal Antibodies ◽  
Chondroitin Sulfate Proteoglycans ◽  
Distal Stump ◽  
Double Labeling ◽  
Rat Sciatic Nerve

Using a glial hyaluronate-binding protein as a probe, monoclonal antibodies against versican and ABC digested chondroitin sulfate proteoglycans, and polyclonal antibodies against laminin, we localized these extracellular matrix (ECM) components in the endoneurium of the adult rat sciatic nerve. During Wallerian degeneration caused by nerve crushing, the staining pattern of these ECM elements changed dramatically. In the first stages and up to 5 days after injury, the tubular endoneurial structures remained the same as in control nerves. Ten days after crush, the bands of Büngner formed by proliferating Schwann cells in the distal stump of crushed nerves stained diffusely for hyaluronate, laminin, and chondroitin sulfate. Regenerating axons were demonstrated in this location by double-labeling experiments with neurofilament antibodies. Conversely, staining with antibodies against versican, a hyaluronate binding proteoglycan, was reduced and the bands of Büngner were not stained. After 30 days the endoneurial tubes made their reappearance and, as in normal nerve, they stained for hyaluronate, laminin, versican, and chondroitin sulfate. It is concluded that proliferating Schwann cells in peripheral nerve undergoing Wallerian degeneration are capable of producing several endoneurial ECM constituents, versican being a notable exception.

scholarly journals Degradation of extracellular chondroitin sulfate delays recovery of network activity after perturbation

2015 ◽  
Vol 114 (2) ◽  
pp. 1346-1352 ◽  
Author(s):  
Amber E. Hudson ◽  
Clare Gollnick ◽  
Jean-Philippe Gourdine ◽  
Astrid A. Prinz
Keyword(s):  
Extracellular Matrix ◽  
Chondroitin Sulfate ◽  
Neural Circuitry ◽  
Model System ◽  
Chondroitin Sulfate Proteoglycans ◽  
Network Activity ◽  
Neuronal Circuit ◽  
Cancer Borealis ◽  
Cellular Effects

Chondroitin sulfate proteoglycans (CSPGs) are widely studied in vertebrate systems and are known to play a key role in development, plasticity, and regulation of cortical circuitry. The mechanistic details of this role are still elusive, but increasingly central to the investigation is the homeostatic balance between network excitation and inhibition. Studying a simpler neuronal circuit may prove advantageous for discovering the mechanistic details of the cellular effects of CSPGs. In this study we used a well-established model of homeostatic change after injury in the crab Cancer borealis to show first evidence that CSPGs are necessary for network activity homeostasis. We degraded CSPGs in the pyloric circuit of the stomatogastric ganglion with the enzyme chondroitinase ABC (chABC) and found that removal of CSPGs does not influence the ongoing rhythm of the pyloric circuit but does limit its capacity for recovery after a networkwide perturbation. Without CSPGs, the postperturbation rhythm is slower than in controls and rhythm recovery is delayed. In addition to providing a new model system for the study of CSPGs, this study suggests a wider role for CSPGs, and perhaps the extracellular matrix in general, beyond simply plastic reorganization (as observed in mammals) and into a foundational regulatory role of neural circuitry.

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