EPHA-mediated growth cone collapse

Stable Identifier
Homo sapiens
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EPH/Ephrin signaling is coupled to Rho family GTPases such as Rac, Rho and Cdc42 that connect bidirectional receptor-ligand interactions to changes in the actin cytoskeleton (Noren & Pasquale 2004, Groeger & Nobes 2007). RHOA regulates actin dynamics and is involved in EPHA-induced growth cone collapse. This is mediated by ephexins. Ephexin, a guanine nucleotide exchange factor for Rho GTPases, interacts with the EPHA kinase domain and its subsequent activation differentially affects Rho GTPases, such that RHOA is activated, whereas Cdc42 and Rac1 are inhibited. Activation of RHOA, and inhibition of Cdc42 and Rac, shifts actin cytoskeleton to increased contraction and reduced expansion leading to growth-cone collapse (Shamah et al. 2001, Sahin et al. 2005). The activation of EPH receptors in growing neurons typically, but not always, leads to a growth cone collapse response and retraction from an ephrin-expressing substrate (Poliakov et al. 2004, Pasquale 2005). EPHA-mediated repulsive responses prevent axons from growing into regions of excessive ephrin-A concentration, such as the posterior end of the superior colliculus (Pasquale 2005).

Literature References
PubMed ID Title Journal Year
17300218 Co-operative Cdc42 and Rho signalling mediates ephrinB-triggered endothelial cell retraction

Groeger, G, Nobes, CD

Biochem. J. 2007
15848799 Eph-dependent tyrosine phosphorylation of ephexin1 modulates growth cone collapse

Debant, A, Greenberg, ME, Corfas, G, Lin, MZ, Wright, TM, Schmidt, S, Cowan, CW, Krull, CE, Sahin, M, Hu, L, Shamah, SM, Goldberg, JL, Poucher, H, Greer, PL, O'connell, S, Eberhart, J

Neuron 2005
15093606 Eph receptor-ephrin bidirectional signals that target Ras and Rho proteins

Pasquale, EB, Noren, NK

Cell. Signal. 2004
15928710 Eph receptor signalling casts a wide net on cell behaviour

Pasquale, EB

Nat. Rev. Mol. Cell Biol. 2005
11336673 EphA receptors regulate growth cone dynamics through the novel guanine nucleotide exchange factor ephexin

Hu, L, Sahin, M, Debant, A, Corfas, G, Bazalakova, M, Goldberg, JL, Greenberg, ME, Lin, MZ, Shamah, SM, Estrach, S, Neve, RL

Cell 2001
15469835 Diverse roles of eph receptors and ephrins in the regulation of cell migration and tissue assembly

Poliakov, A, Wilkinson, DG, Cotrina, M

Dev. Cell 2004
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