Ganglioside GM1 Enhances Induction by Nerve Growth Factor of a Putative Dimer of TrkA

Farooqui, Tahira; Franklin, Teresa K.; Pearl, Dennis K.; Yates, Allan J.

doi:10.1046/j.1471-4159.1997.68062348.x

Cited by 104 publications

(76 citation statements)

References 30 publications

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“…We should note that previous reports have suggested that ganglioside G M1 induces Trk phosphorylation by itself and that it potentiates NGF-induced TrkA phosphorylation (Ferrari et al, 1995;Mutoh et al, 1995;Farooqui et al, 1997). We were able to detect a modest increase in TrkB phosphorylation in response to ganglioside G M1 only after high exposure of the autoradiography films (data not shown).…”

Section: Discussionsupporting

confidence: 52%

The Tyrosine Kinase Fyn Determines the Localization of TrkB Receptors in Lipid Rafts

Pereira¹,

Chao²

2007

J. Neurosci.

124

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Section: Discussionsupporting

confidence: 52%

The Tyrosine Kinase Fyn Determines the Localization of TrkB Receptors in Lipid Rafts

Pereira¹,

Chao²

2007

J. Neurosci.

124

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“…In particular, a striking correlation between ganglioside expression and neuritogenesis has previously been established (Hogan et al, 1988;Rosenberg et al, 1992). The regulatory role of such lipids is usually attributed to their ability to form microdomains in cell membranes (Masserini et al, 1988), allowing for selective sorting of polarized neuronal structures (Hogan et al, 1988;van Echten and Sandhoff, 1989) or for dimerization-induced activation of growth factor receptors (Farooqui et al, 1997). It has been proposed that biochemical engineering of the side chain sialic acid might activate β1 integrins thus increasing binding to ECM molecules and favoring neuritogenesis (Buttner et al, 2002).…”

Section: Figmentioning

confidence: 99%

Sialic acid residues on astrocytes regulate neuritogenesis by controlling the assembly of laminin matrices

Freire

Gomes

Jotha-Mattos

et al. 2004

Journal of Cell Science

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In the developing nervous system migrating neurons and growing axons are guided by diffusible and/or substrate-bound cues, such as extracellular matrix-associated laminin. In a previous work we demonstrated that laminin molecules could self-assemble in two different manners, giving rise to matrices that could favor either neuritogenesis or proliferation of cortical precursor cells. We investigated whether the ability of astrocytes to promote neuritogenesis of co-cultivated neurons was modulated by the assembling mode of the laminin matrix secreted by them. We compared the morphologies and neuritogenic potentials of laminin deposited by in vitro-differentiated astrocytes obtained from embryonic or neonatal rat brain cortices. We showed that, while permissive astrocytes derived from embryonic brain produced a flat laminin matrix that remained associated to the cell surface, astrocytes derived from newborn brain secreted a laminin matrix resembling a fibrillar web that protruded from the cell plane. The average neurite lengths obtained for E16 neurons cultured on each astrocyte layer were 198±22 and 123±13 μm, respectively. Analyses of surface-associated electrostatic potentials revealed that embryonic astrocytes presented a pI of -2.8, while in newborn cells this value was -3.8. Removal of the sialic acid groups on the embryonic monolayer by neuraminidase treatment led to the immediate release of matrix-associated laminin. Interestingly, laminin reassembled 1 hour after neuraminidase removal converted to the features of the newborn matrix. Alternatively, treatment of astrocytes with the cholesterol-solubilizing detergent methyl-β-cyclodextrin also resulted in release of the extracellular laminin. To test the hypothesis that sialic-acid-containing lipids localized at cholesterol-rich membrane domains could affect the process of laminin assembly, we devised a cell-free assay where laminin polymerization was carried out over artificial lipid films. Films of either a mixture of gangliosides or pure ganglioside GT1b induced formation of matrices of morpho-functional features similar to the matrices deposited by embryonic astrocytes. Conversely, films of phosphatidylcholine or ganglioside GM1 led to the formation of bulky laminin aggregates that lacked a defined structure. We propose that the expression of negative lipids on astrocytes can control the extracellular polymerization of laminin and, consequently, the permissivity to neuritogenesis of astrocytes during development.

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“…In addition, it has been postulated that GM1 may activate TrkA by inducing receptor dimerization (40). To test whether either one of these mechanisms may account for the ability of GM1 to induce Trk tyrosine phosphorylation, NIH-3T3 cells were transfected with an expression vector containing p70 trk , a chimeric receptor consisting of the extracellular domain of the TNF receptor and the transmembrane and intracellular domains of TrkA (36).…”

Section: Fig 1 Gm1 Activates Trk Tyrosine Phosphorylation Niha (A)mentioning

confidence: 99%

Gangliosides Activate Trk Receptors by Inducing the Release of Neurotrophins

Rabin

Bachis

Mocchetti

2002

Journal of Biological Chemistry

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We used NIH-3T3 fibroblasts expressing the different Trk receptors to examine whether GM1 ganglioside and its semisynthetic derivative LIGA20 activate various neurotrophin receptors. GM1 induced autophosphorylation of TrkC more potently than TrkA or TrkB receptors. In contrast, LIGA20 activated TrkB tyrosine phosphorylation only. Therefore, Scatchard analysis was performed to determine whether GM1 binds to TrkC. GM1 failed to displace neurotrophin-3 binding, suggesting that this ganglioside does not act as a ligand for Trk receptors. In addition, GM1 failed to induce autophosphorylation of a chimeric receptor consisting of the extracellular domain of the tumor necrosis factor receptor and the intracellular domain of TrkA, suggesting that GM1 does not affect the tyrosine kinase domain. We next determined whether GM1 induces the release of neurotrophins from fibroblast cells. GM1 induced a rapid and significant increase in the amount of neurotrophin-3, but not other neurotrophins. This effect was independent of the presence of Trk because K252a did not prevent GM1-mediated release of neurotrophin-3. Moreover, GM1-mediated TrkC autophosphorylation was blocked by TrkC-IgG (but not TrkB-IgG) receptor bodies, further suggesting that GM1 activates TrkC by inducing the release of neurotrophin-3. This hypothesis was also tested in cultured cerebellar granule cells. GM1 induced neurotrophin-3 (but not brain-derived neurotrophic factor or nerve growth factor) release. In contrast, LIGA20 increased the secretion of brain-derived neurotrophic factor. Our data show that gangliosides may activate different Trk receptors by differentially affecting the release of neurotrophins.Gangliosides constitute a heterogeneous family of sialic acidcontaining glycosphingolipids found in relative abundance in the nervous system (1, 2), where they influence the development and/or differentiation of neurons (3-5). Interest in these molecules has grown since the discovery that gangliosides display neurotrophic properties in neurons of the central nervous system both in vitro and in vivo. Indeed, the monosialotetrahexosylganglio (GM1) 1 prevents the dramatic loss of cholinergic neurons subsequent to hippocampal ablation or cortical lesion (6 -9). GM1 also stimulates the regeneration of dopaminergic neurons (10), improves cell survival in injured substantia nigra (11), and ameliorates the abnormal motor responses in animals treated with the dopamine neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (12). Moreover, GM1 and other gangliosides have been shown to possess a neuroprotective action against excitatory amino acid toxicity in vitro (13-15) and after stroke or brain ischemia (16, 17) as well as after spinal cord injury (18). Despite these findings, the mechanisms of ganglioside trophic activity are still unclear. Potential substrates of GM1 that would explain its neurotrophic effects are the neurotrophins and their receptors. The neurotrophin family of neurotrophic factors includes nerve growth factor (NGF), brain-derived neurotrophi...

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Ganglioside GM1 Enhances Induction by Nerve Growth Factor of a Putative Dimer of TrkA

Cited by 104 publications

References 30 publications

The Tyrosine Kinase Fyn Determines the Localization of TrkB Receptors in Lipid Rafts

The Tyrosine Kinase Fyn Determines the Localization of TrkB Receptors in Lipid Rafts

Sialic acid residues on astrocytes regulate neuritogenesis by controlling the assembly of laminin matrices

Gangliosides Activate Trk Receptors by Inducing the Release of Neurotrophins

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