Myelin-associated Glycoprotein Interacts with Neurons via a Sialic Acid Binding Site at ARG118 and a Distinct Neurite Inhibition Site

Tang, Song; Shen, Ying Jing; DeBellard, Maria Elena; Mukhopadhyay, Gauranga; Salzer, James L.; Crocker, Paul R.; Filbin, Marie T.

doi:10.1083/jcb.138.6.1355

Cited by 137 publications

(131 citation statements)

References 42 publications

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“…It is also a sialic acid-binding protein, and its first four Ig-like domains are homologous to those of other sialic acid binding, Ig-like LECTINS (Siglecs), so it is also a member of the Siglec family (Siglec4a) 24 . The sialic acid binding capabilities of Mag are not essential for it to exert inhibition 25 , but they are likely to potentiate the effect (see later in text and BOX 2). Mag is found in both the CNS and the PNS, where it is located in the periaxonal membrane, and is therefore ideally placed to interact with an axonal receptor.…”

Section: Receptors For Inhibitors Of Axonal Growthmentioning

confidence: 99%

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

2003

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Section: Receptors For Inhibitors Of Axonal Growthmentioning

confidence: 99%

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

2003

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“…It has also been reported that soluble dMAG species secreted from damaged white matter are able to inhibit axonal regeneration (Tang et al, 2001;Tang et al, 1997b). This inhibition appears to require both the presence of a sialic acid binding site at R118 within the first Ig domain as well as a second, unknown site (Tang et al, 1997a). The R118 site is present within an RGD sequence (Fig.…”

Section: Mmp-7 Generated Mag Fragments Inhibit Neuronal Process Outgrmentioning

confidence: 80%

“…Cleavage at either Leu 509 or Met 234 would potentially release an N terminal fragment that includes the sialic-acid binding domain which is critical to the neurite outgrowth inhibitory effect of dMAG (Tang et al, 1997a). To assess the bioactivity of soluble MMP-generated MAG fragments, specifically the effects on neuronal process growth, we used Campenot chambers (Campenot, 1977).…”

Section: Mmp-7 Generated Mag Fragments Inhibit Neuronal Process Outgrmentioning

confidence: 99%

Cleavage of myelin associated glycoprotein by matrix metalloproteinases

Milward

Kim

Szklarczyk

et al. 2008

Journal of Neuroimmunology

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Derivative myelin associated glycoprotein (dMAG) results from proteolysis of transmembrane MAG and can inhibit axonal growth. We have tested the ability of certain matrix metalloproteinases Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access

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“…It was previously shown that soluble MAG, released in abundance from myelin and found in vivo, and MAG-Fc could potently inhibit axonal growth. 12,13 Our results revealed that soluble MAG-Fc (25 mg/ml) triggered Rap1 activation from 10 min to 4 h after its addition into the medium (Figure 1a). In contrast, the activity of Ras, another member of the Ras family of small G proteins, was suppressed transiently and returned to the control level at 4 h ( Figure 1a).…”

Section: Resultsmentioning

confidence: 84%

“…12,13 It is also possible that the transport of p75 in complex with Rap1 does not require the internalization of MAG.…”

Section: Discussionmentioning

confidence: 99%

Rap1 is involved in the signal transduction of myelin-associated glycoprotein

et al. 2007

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Myelin-associated glycoprotein (MAG) is a well-characterized axon growth inhibitor in the adult vertebrate nervous system. Several signals that play roles in inhibiting axon growth have been identified. Here, we report that soluble MAG induces activation of Rap1 in postnatal cerebellar granule neurons (CGNs) and dorsal root ganglion (DRG) neurons. The p75 receptor associates with activated Rap1 and is internalized in response to MAG. After MAG is applied to the distal axons of the sciatic nerves, the activated Rap1, internalized p75 receptor, and MAG are retrogradely trafficked via axons to the cell bodies of the DRG neurons. Rap1 activity is required for survival of the DRG neurons as well as CGNs when treated with MAG. Myelin-associated glycoprotein (MAG) is a member of the I-type lectin subgroup of the immunoglobulin (Ig) gene superfamily and is expressed exclusively by myelinating cells where it is enriched in the adaxonal membrane of the myelin internode. MAG inhibits neurite outgrowth from the adult dorsal root ganglion (DRG) and the postnatal ages of the cerebellar, retinal, spinal, hippocampal, and superior cervical ganglion neurons. 1,2 To date, two additional neurite growth inhibitors that are expressed by oligodendrocytes and myelinated fiber tracts have been identified. 3 These are Nogo and oligodendrocyte-myelin glycoprotein. All these proteins act on neurons through the Nogo receptor complex. This is a trimolecular complex comprising the Nogo receptor, Lingo-1, and p75/Troy. 4 A key intracellular effector for neurite growth inhibitory signaling by myelin was previously shown to be the small guanine nucleoside triphosphatase, RhoA. In its active GTP-bound form, RhoA rigidifies the actin cytoskeleton, thereby inhibiting axon elongation and mediating growth cone collapse. RhoA is activated by these proteins through a p75-dependent mechanism, thus inhibiting neurite outgrowth from the postnatal sensory neurons and cerebellar neurons. 5,6 It was also demonstrated that conventional protein kinase C (PKC), including PKC-a, -b, and -g, was activated by the neurite growth inhibitory proteins, and the inhibition of conventional PKC eliminated the effect of these proteins on neurite outgrowth. 7,8 In addition, phosphorylation of the epidermal growth factor (EGF) receptor is triggered by these myelin-derived inhibitors and is necessary for the inhibitory effect. 9 These multiple signals are responsible for the effects of the myelin-derived inhibitors at least in vitro.In addition to the role of MAG in axon regeneration, experiments with MAG-deficient mice implicate this protein in regulating axonal caliber and the levels of neurofilament spacing in mature myelinated fibers. 10 MAG is suggested to modulate the maturation and viability of myelinated axons. These findings suggest the diverse functions of MAG in the nervous system.In the course of identifying signals downstream of MAG, we found that Rap1 is activated in response to soluble MAG. Rap1 is a member of the Ras family of small guanine nucleotidebinding ...

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Myelin-associated Glycoprotein Interacts with Neurons via a Sialic Acid Binding Site at ARG118 and a Distinct Neurite Inhibition Site

Cited by 137 publications

References 42 publications

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

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

Cleavage of myelin associated glycoprotein by matrix metalloproteinases

Rap1 is involved in the signal transduction of myelin-associated glycoprotein

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