Tsc2-Rheb signaling regulates EphA-mediated axon guidance.
Saved in:
| Title: | Tsc2-Rheb signaling regulates EphA-mediated axon guidance. |
|---|---|
| Authors: | Nie, Duyu, Di Nardo, Alessia, Han, Juliette M., Baharanyi, Hasani, Kramvis, Ioannis, Huynh, ThanhThao, Dabora, Sandra, Codeluppi, Simone, Pandolfi, Pier Paolo, Pasquale, Elena B., Sahin, Mustafa |
| Source: | Nature Neuroscience. Feb2010, Vol. 13 Issue 2, p163-172. 10p. 3 Diagrams, 5 Graphs. |
| Subjects: | Tuberous sclerosis, Genetic mutation, Proteins, Guanosine triphosphatase, Axons |
| Abstract: | Tuberous sclerosis complex is a disease caused by mutations in the TSC1 or TSC2 genes, which encode a protein complex that inhibits mTOR kinase signaling by inactivating the Rheb GTPase. Activation of mTOR promotes the formation of benign tumors in various organs and the mechanisms underlying the neurological symptoms of the disease remain largely unknown. We found that Tsc2 haploinsufficiency in mice caused aberrant retinogeniculate projections that suggest defects in EphA receptor–dependent axon guidance. We also found that EphA receptor activation by ephrin-A ligands in neurons led to inhibition of extracellular signal–regulated kinase 1/2 (ERK1/2) activity and decreased inhibition of Tsc2 by ERK1/2. Thus, ephrin stimulation inactivates the mTOR pathway by enhancing Tsc2 activity. Furthermore, Tsc2 deficiency and hyperactive Rheb constitutively activated mTOR and inhibited ephrin-induced growth cone collapse. Our results indicate that TSC2-Rheb-mTOR signaling cooperates with the ephrin-Eph receptor system to control axon guidance in the visual system. [ABSTRACT FROM AUTHOR] |
| Copyright of Nature Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
Be the first to leave a comment!
