Lipid Raft-Excluded GFRα1/Ret Fails to Transmit GDNF Signaling<i>In Vivo</i>

Morales, Daniel

doi:10.1523/jneurosci.4155-15.2016

Cited by 4 publications

(3 citation statements)

References 22 publications

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“…One may also get at unresolved questions by creating mutant mice carrying structurally modified molecules. This strategy has been applied to guidance cue receptors to, for example, examine the role of proteolytic processing (Gatto, Morales, Kania, & Klein, ) or of specific membrane domain targeting (Tsui, Gabreski, Hein, & Pierchala, ; see also Morales, ). Producing a mouse expressing a modified, membrane‐bound netrin1, as in the fly mentioned above, would reveal whether all of the cue's activities are, indeed, short‐range.…”

Section: Discussionmentioning

confidence: 99%

A new model for netrin1 in commissural axon guidance

Morales

2017

J of Neuroscience Research

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Now-classic experiments characterized netrin1 as a major player in commissural axon guidance in the spinal cord. The data suggest a chemotactic model in which netrin1 expression in the floor plate forms a concentration gradient that attracts commissural axons. New research published independently in Neuron and in Nature tests this model by deleting netrin1 specifically in the floor plate. Surprisingly, these conditional mutant mice have no overt commissure defects. The authors report that netrin1 decorates the pial surface of the spinal cord and hindbrain, likely deposited by radial processes of progenitor cells in the ventricular zone. They find that deletion of the cue exclusively in the ventricular zone causes commissural axons to take aberrant trajectories, suggesting a short range, haptotactic guidance mechanism as opposed to chemotaxis. This minireview aims to summarize the classic and the new findings and offer some interpretations of the data.

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Section: Discussionmentioning

confidence: 99%

A new model for netrin1 in commissural axon guidance

Morales

2017

J of Neuroscience Research

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“…GDNF has a unique receptor system that consists of the transmembrane signal transduction receptor RET and the ligand binding receptor GFRα1 [12] . Lipid rafts play a vital role in the transmission of GDNF signals [13][14][15] . Lipid rafts are highly dynamic membrane microdomains enriched in cholesterol and spingolipids, and they are in liquid-ordered (Lo) phases with lower membrane uidity than surrounding cell membranes [16,17] .…”

Section: Introductionmentioning

confidence: 99%

“…We and others showed that in the absence of GDNF, the signal transduction receptor RET is mainly located outside of lipid rafts [18] . After stimulation with GDNF, RET is translocated into lipid rafts, and multiple downstream effectors are recruited to activate RAS/Erk, PI3K/Akt and other signal transduction pathways involved in the regulation of cell survival, differentiation, migration, growth and other biological processes [13,14] .…”

Section: Introductionmentioning

confidence: 99%

Monosialoganglioside GM1 Deficiency Inhibits the Neurotrophic Effects of GDNF by Disrupting Lipid Raft Assembly

Jiang

Zhou

Zhang

et al. 2021

Preprint

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Recent studies have shown that monosialoganglioside GM1 deficiency can inhibit the signal transduction process of glial cell line-derived neurotrophic factor (GDNF), which plays an important role in the pathogenesis of Parkinson's disease (PD). However, its specific mechanism still needs to be explored. We inhibited the expression of GM1 by treating cells with D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP). CCK-8 assay, EdU cell proliferation assay and Western blot assay were used to evaluate the effect of GM1 deficiency on the proliferation and differentiation of SH-SY5Y cells induced by GDNF and on the GDNF-RET signaling pathway. Lipid rafts were isolated by Triton X-100 solubilization and OptiPrepTM density gradient centrifugation. The alterations of lipid raft assembly and the translocation of RET into lipid rafts were evaluated after PDMP treatment. We found that PDMP treatment inhibited the proliferation and differentiation of SH-SY5Y cells induced by GDNF and reduced the phosphorylation of RET and its downstream signaling molecules Erk and Akt. In addition, after PDMP treatment, caveolin-1 and flotillin-1, the prototypical markers of lipid rafts, diffused from lipid rafts to non-lipid raft microdomains, and GDNF-induced RET translocation into lipid rafts was also reduced. These alterations could be partially reversed by adding exogenous GM1. Our results suggest that ganglioside GM1 deficiency could compromise the neurotrophic effects and signals downstream of GDNF by altering the assembly of lipid raft membrane microdomains.

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Intracellular RET signaling pathways activated by GDNF

Kawai

Takahashi

2020

Cell Tissue Res

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Lipid Raft-Excluded GFRα1/Ret Fails to Transmit GDNF SignalingIn Vivo

Cited by 4 publications

References 22 publications

A new model for netrin1 in commissural axon guidance

A new model for netrin1 in commissural axon guidance

Monosialoganglioside GM1 Deficiency Inhibits the Neurotrophic Effects of GDNF by Disrupting Lipid Raft Assembly

Intracellular RET signaling pathways activated by GDNF

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