scholarly journals Kindlin-1 Enhances Axon Growth on Inhibitory Chondroitin Sulfate Proteoglycans and Promotes Sensory Axon Regeneration

2012 ◽  
Vol 32 (21) ◽  
pp. 7325-7335 ◽  
Author(s):  
C. L. Tan ◽  
M. R. Andrews ◽  
J. C. F. Kwok ◽  
T. G. P. Heintz ◽  
L. F. Gumy ◽  
...  
Keyword(s):  
Chondroitin Sulfate ◽  
Axon Regeneration ◽  
Axon Growth ◽  
Chondroitin Sulfate Proteoglycans ◽  
Sensory Axon

scholarly journals Inhibition of PTEN activity promotes IB4-positive sensory neuronal axon growth

2020 ◽  
Author(s):  
Li-Yu Zhou ◽  
Feng Han ◽  
Shi-Bin Qi ◽  
Jin-Jin Ma ◽  
Yan-Xia Ma ◽  
...  
Keyword(s):  
Nervous System ◽  
Sensory Neurons ◽  
Strong Evidence ◽  
Axon Regeneration ◽  
Axon Growth ◽  
Clinical Problem ◽  
Sensory Axon ◽  
Nerve Injuries ◽  
Critical Process ◽  
Common Clinical Problem

AbstractTraumatic nerve injuries have become a common clinical problem, and axon regeneration is a critical process in the successful functional recovery of the injured nervous system. In this study, we found that peripheral axotomy reduce total PTEN expression in adult sensory neurons, however, it did not alter the expression level of PTEN in IB4-positive sensory neurons. Additionally, our results indicate that the artificial inhibition of PTEN markedly promotes adult sensory axon regeneration, including IB4-positive neuronal axon growth. Thus, our results provide strong evidence that PTEN is a prominent repressor of adult sensory axon regeneration, especially in IB4-positive neurons.

scholarly journals Integrin Activation Promotes Axon Growth on Inhibitory Chondroitin Sulfate Proteoglycans by Enhancing Integrin Signaling

2011 ◽  
Vol 31 (17) ◽  
pp. 6289-6295 ◽  
Author(s):  
C. L. Tan ◽  
J. C. F. Kwok ◽  
R. Patani ◽  
C. ffrench-Constant ◽  
S. Chandran ◽  
...  
Keyword(s):  
Chondroitin Sulfate ◽  
Axon Growth ◽  
Chondroitin Sulfate Proteoglycans ◽  
Integrin Signaling ◽  
Integrin Activation

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 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 N6-methyladenine DNA demethylase ALKBH1 regulates mammalian axon regeneration

2020 ◽  
Author(s):  
Qiao Li ◽  
Cheng Qian ◽  
Harry Feng ◽  
Tyger Lin ◽  
Ying Huang ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Neuronal Development ◽  
Axon Regeneration ◽  
Physiological Function ◽  
Axon Growth ◽  
Epigenetic Mechanism ◽  
Sensory Axon ◽  
Functional Roles

AbstractRecent studies have shown that DNA N6-methyladenine (N6-mA) modification is emerging to be a novel and important epigenetic regulator of mammalian gene transcription. Several studies demonstrated DNA N6-mA in human or rodents was regulated by methyltransferase N6AMT1 and demethylase ALKBH1. Moreover, studies in mouse brain or human glioblastoma cells showed that reduced level of N6-mA or higher level of ALKBH1 was correlated with up regulated levels of genes associated with neuronal development. We thus investigated the functional roles of ALKBH1 in sensory axon regeneration. Our results showed that ALKBH1 regulated the level of N6-mA in sensory neurons, and upon peripheral nerve injury ALKBH1 was up regulated in mouse sensory neurons. Functionally, knocking down ALKBH1 in sensory neurons resulted in reduced axon regeneration in vitro and in vivo, which could be rescued by simultaneously knocking down N6AMT1. Moreover, knocking down ALKBH1 led to decreased levels of many neurodevelopment regulatory genes, including neuritin that is well known to enhance axon growth and regeneration. Our study not only revealed a novel physiological function of DNA N6-mA, but also identified a new epigenetic mechanism regulating mammalian axon regeneration.Significance StatementThe study demonstrated that DNA N6-methyladenine (N6-mA) modification played important roles in regulation of sensory axon regeneration, likely through controlling the expression of neurodevelopmental associated genes. The results will add new evidence about the physiological function of DNA N6-mA and its regulatory demethylase ALKBH1 in neurons.

Chondroitin sulfate proteoglycans as mediators of axon growth and pathfinding

1997 ◽  
Vol 290 (2) ◽  
pp. 343-348 ◽  
Author(s):  
Richard U. Margolis ◽  
Renée K. Margolis
Keyword(s):  
Chondroitin Sulfate ◽  
Axon Growth ◽  
Chondroitin Sulfate Proteoglycans

scholarly journals The MAP3Ks DLK and LZK direct diverse responses to axon damage in zebrafish peripheral neurons

2021 ◽  
Author(s):  
Kadidia Pemba Adula ◽  
Matthew Shorey ◽  
Vasudha Chauhan ◽  
Khaled Nassman ◽  
Shu-Fan Chen ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Leucine Zipper ◽  
Axon Regeneration ◽  
Neuronal Cell ◽  
Axon Growth ◽  
Sensory Axon ◽  
Axon Injury ◽  
Peripheral Neurons ◽  
Sensory Axons ◽  
Axon Damage

The MAP3Ks Dual Leucine Kinase (DLK) and Leucine Zipper Kinase (LZK) are essential mediators of axon damage responses, but their responses are varied, complex, and incompletely understood. To characterize their functions in axon injury, we generated zebrafish mutants of each gene, labeled motor neurons (MN) and touch-sensing neurons in live zebrafish, precisely cut their axons with a laser, and assessed the ability of mutant axons to regenerate. DLK and LZK were required redundantly and cell autonomously for axon regeneration in MNs, but not in larval Rohon-Beard (RB) or adult dorsal root ganglion (DRG) sensory neurons. Surprisingly, in dlk lzk double mutants, the spared branches of wounded RB axons grew excessively, suggesting that these kinases inhibit regenerative sprouting in damaged axons. Uninjured trigeminal sensory axons also grew excessively in mutants when neighboring neurons were ablated, indicating that these MAP3Ks are general inhibitors of sensory axon growth. These results demonstrate that zebrafish DLK and LZK promote diverse injury responses, depending on the neuronal cell identity and type of axonal injury.

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