p120RasGAP Protein Mediates Netrin-1 Protein-induced Cortical Axon Outgrowth and Guidance
Copyright policy )p120RasGAP Protein Mediates Netrin-1 Protein-induced Cortical Axon Outgrowth and Guidance
The receptor deleted in colorectal cancer (DCC) mediates the attraction of growing axons to netrin-1 during brain development. In response to netrin-1 stimulation, DCC becomes a signaling platform to recruit proteins that promote axon outgrowth and guidance. The Ras GTPase-activating protein (GAP) p120RasGAP inhibits Ras activity and mediates neurite retraction and growth cone collapse in response to repulsive guidance cues. Here we show an interaction between p120RasGAP and DCC that positively regulates netrin-1-mediated axon outgrowth and guidance in embryonic cortical neurons. In response to netrin-1, p120RasGAP is recruited to DCC in growth cones and forms a multiprotein complex with focal adhesion kinase and ERK. We found that Ras/ERK activities are elevated aberrantly in p120RasGAP-deficient neurons. Moreover, the expression of p120RasGAP Src homology 2 (SH2)-SH3-SH2 domains, which interact with the C-terminal tail of DCC, is sufficient to restore netrin-1-dependent axon outgrowth in p120RasGAP-deficient neurons. We provide a novel mechanism that exploits the scaffolding properties of the N terminus of p120RasGAP to tightly regulate netrin-1/DCC-dependent axon outgrowth and guidance.
- McGill University Health Centre Canada
- Montreal Neurological Institute and Hospital Canada
- McGill University Canada
Cerebral Cortex, Neurons, Nerve Tissue Proteins, Netrin-1, DCC Receptor, Embryo, Mammalian, Axons, Peptide Fragments, Protein Transport, HEK293 Cells, Amino Acid Substitution, Animals, Humans, Mutant Proteins, Protein Interaction Domains and Motifs, RNA Interference, Nerve Growth Factors, Chickens, Cells, Cultured, Glutathione Transferase
Cerebral Cortex, Neurons, Nerve Tissue Proteins, Netrin-1, DCC Receptor, Embryo, Mammalian, Axons, Peptide Fragments, Protein Transport, HEK293 Cells, Amino Acid Substitution, Animals, Humans, Mutant Proteins, Protein Interaction Domains and Motifs, RNA Interference, Nerve Growth Factors, Chickens, Cells, Cultured, Glutathione Transferase
selected citations These citations are derived from selected sources.This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).10 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Average influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!