Oligodendrocyte‐myelin glycoprotein (OMgp) is an inhibitor of neurite outgrowth

Kottis, Vicky; Thibault, Pierre; Mikol, Daniel D.; Xiao, Zhicheng; Zhang, Rulin; Dergham, Pauline; Braun, Peter E.

doi:10.1046/j.1471-4159.2002.01146.x

Cited by 241 publications

(150 citation statements)

References 21 publications

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“…These results are consistent with several earlier reports that integrin activation could enhance axon growth from neurons in vitro, even when cultured in the presence of inhibitory molecules such as amino-Nogo or aggrecan (Ivins et al, 2000;Lein et al, 2000;Hu and Strittmatter, 2008;Tan et al, 2011), and also with our demonstration that expression of a tenascin-binding integrin can promote axon regeneration (Andrews et al, 2009). CNS injuries cause an upregulation of myelin-related inhibitors (e.g., Nogo, oligodendrocyte myelin glycoprotein, myelin-associated glycoprotein) (McKerracher et al, 1994;Mukhopadhyay et al, 1994;GrandPré et al, 2000GrandPré et al, , 2002Prinjha et al, 2000;Kottis et al, 2002;Wang et al, 2002) and CSPGs (e.g., aggrecan, brevican, phosphacan, versican), which impair regenerative responses (Jaworski et al, 1999;McKeon et al, 1999;Asher et al, 2000;Afshari et al, 2010). Our experiment suggests that integrin activation might be a general method to overcome these inhibitory effects and promote axon regeneration in vivo.…”

Section: Differential Effects Of Kindlin-1 and -2supporting

confidence: 93%

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

Tan¹,

Andrews²,

Kwok³

et al. 2012

J. Neurosci.

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Growing and regenerating axons need to interact with the molecules in the extracellular matrix as they traverse through their environment. An important group of receptors that serve this function is the integrin superfamily of cell surface receptors, which are evolutionarily conserved ␣␤ heterodimeric transmembrane proteins. The function of integrins is controlled by regulating the affinity for ligands (also called "integrin activation"). Previous results have shown that CNS inhibitory molecules inactivate axonal integrins, while enhancing integrin activation can promote axon growth from neurons cultured on inhibitory substrates. We tested two related molecules, kindlin-1 and kindlin-2 (Fermitin family members 1 and 2), that can activate ␤1, ␤2, and ␤3 integrins, for their effects on integrin signaling and integrin-mediated axon growth in rat sensory neurons. We determined that kindlin-2, but not kindlin-1, is endogenously expressed in the nervous system. Knocking down kindlin-2 levels in cultured sensory neurons impaired their ability to extend axons, but this was partially rescued by kindlin-1 expression. Overexpression of kindlin-1, but not kindlin-2, in cultured neurons increased axon growth on an inhibitory aggrecan substrate. This was found to be associated with enhanced integrin activation and signaling within the axons. Additionally, in an in vivo rat dorsal root injury model, transduction of dorsal root ganglion neurons to express kindlin-1 promoted axon regeneration across the dorsal root entry zone and into the spinal cord. These animals demonstrated improved recovery of thermal sensation following injury. Our results therefore suggest that kindlin-1 is a potential tool for improving axon regeneration after nervous system lesions.

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Section: Differential Effects Of Kindlin-1 and -2supporting

confidence: 93%

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

Tan¹,

Andrews²,

Kwok³

et al. 2012

J. Neurosci.

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“…Omgp contains a leucine-rich repeat (LRR) domain, followed by a C-terminal domain with serine/threonine repeats. In addition, Omgp is the protein that is responsible for the inhibition by the myelin fraction originally termed 'arretin' 31 . Like Mag and Nogo, Omgp induces growth cone collapse and inhibits neurite outgrowth.…”

Section: Box 1 | Regeneration In the Pns Versus The Cnsmentioning

confidence: 99%

Myelin-associated inhibitors of axonal regeneration in the adult mammalian CNS

2003

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“…Indeed, several components from the disrupted myelin and extracellular matrix components produced by reactive astrocytes, microglia, and fibrocytes show strong inhibitory properties on axonal outgrowth and regeneration, limiting the recovery of motor function after injury (Savio and Schwab, 1990;Schnell and Schwab, 1990;McKerracher et al, 1994;Bregman et al, 1995;Davies et al, 1999;Chen et al, 2000;Bradbury et al, 2002;GrandPré et al, 2002;Kottis et al, 2002;Sroga et al, 2003;Silver and Miller, 2004;Yiu and He, 2006;Hellal et al, 2011;Wang et al, 2011). In p53 Ϫ/Ϫ injured cords, aberrant glial proliferation is accompanied by enhanced glial scar formation, as shown by GFAP-and fibronectin-positive scar tissue revealing a bigger reactive astrocyte area around the lesion site and an enlarged lesion core.…”

Section: Discussionmentioning

confidence: 99%

p53 Regulates the Neuronal Intrinsic and Extrinsic Responses Affecting the Recovery of Motor Function following Spinal Cord Injury

et al. 2012

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Following spinal trauma, the limited physiological axonal sprouting that contributes to partial recovery of function is dependent upon the intrinsic properties of neurons as well as the inhibitory glial environment. The transcription factor p53 is involved in DNA repair, cell cycle, cell survival, and axonal outgrowth, suggesting p53 as key modifier of axonal and glial responses influencing functional recovery following spinal injury. Indeed, in a spinal cord dorsal hemisection injury model, we observed a significant impairment in locomotor recovery in p53 Ϫ/Ϫ versus wild-type mice. p53 Ϫ/Ϫ spinal cords showed an increased number of activated microglia/macrophages and a larger scar at the lesion site. Loss-and gain-of-function experiments suggested p53 as a direct regulator of microglia/macrophages proliferation. At the axonal level, p53 Ϫ/Ϫ mice showed a more pronounced dieback of the corticospinal tract (CST) and a decreased sprouting capacity of both CST and spinal serotoninergic fibers. In vivo expression of p53 in the sensorimotor cortex rescued and enhanced the sprouting potential of the CST in p53 Ϫ/Ϫ mice, while, similarly, p53 expression in p53 Ϫ/Ϫ cultured cortical neurons rescued a defect in neurite outgrowth, suggesting a direct role for p53 in regulating the intrinsic sprouting ability of CNS neurons. In conclusion, we show that p53 plays an important regulatory role at both extrinsic and intrinsic levels affecting the recovery of motor function following spinal cord injury. Therefore, we propose p53 as a novel potential multilevel therapeutic target for spinal cord injury.

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Oligodendrocyte‐myelin glycoprotein (OMgp) is an inhibitor of neurite outgrowth

Cited by 241 publications

References 21 publications

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

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

Myelin-associated inhibitors of axonal regeneration in the adult mammalian CNS

p53 Regulates the Neuronal Intrinsic and Extrinsic Responses Affecting the Recovery of Motor Function following Spinal Cord Injury

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