Gene interactions and pathways from curated databases and text-mining
Nat Neurosci 2010, PMID: 20062052

Tsc2-Rheb signaling regulates EphA-mediated axon guidance.

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

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.

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Text Mining Data

extracellular signal regulated kinase 1/2 ⊣ EphA: " 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 "

extracellular signal regulated kinase 1/2 ⊣ ephrin-A: " 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 "

EphA → ephrin-A: " 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 "

mTOR ⊣ Tsc2: " Furthermore, Tsc2 deficiency and hyperactive Rheb constitutively activated mTOR and inhibited ephrin induced growth cone collapse "

mTOR → Rheb: " Furthermore, Tsc2 deficiency and hyperactive Rheb constitutively activated mTOR and inhibited ephrin induced growth cone collapse "

Manually curated Databases

No curated data.