Eph-Dependent Tyrosine Phosphorylation of Ephexin1 Modulates Growth Cone Collapse
نویسندگان
چکیده
Ephs regulate growth cone repulsion, a process controlled by the actin cytoskeleton. The guanine nucleotide exchange factor (GEF) ephexin1 interacts with EphA4 and has been suggested to mediate the effect of EphA on the activity of Rho GTPases, key regulators of the cytoskeleton and axon guidance. Using cultured ephexin1-/- mouse neurons and RNA interference in the chick, we report that ephexin1 is required for normal axon outgrowth and ephrin-dependent axon repulsion. Ephexin1 becomes tyrosine phosphorylated in response to EphA signaling in neurons, and this phosphorylation event is required for growth cone collapse. Tyrosine phosphorylation of ephexin1 enhances ephexin1's GEF activity toward RhoA while not altering its activity toward Rac1 or Cdc42, thus changing the balance of GTPase activities. These findings reveal that ephexin1 plays a role in axon guidance and is regulated by a switch mechanism that is specifically tailored to control Eph-mediated growth cone collapse.
منابع مشابه
Supplemental Data Eph-Dependent Tyrosine Phosphorylation of ephexin1 Modulates Growth Cone Collapse
Generation of Ephexin1−/− Mice Ephexin1 cDNA was used to probe a λ phage 129/SvJ mouse genomic DNA library, and a 12.5 kB SalI-BsrB1 fragment from a positive clone was subcloned into pBluescriptKS to generate pMSG. A BamHI-LoxP1 double stranded oligo was inserted into a BamHI site 1kb upstream of the translation initiation site of ephexin1. A LoxP2hrGFP-NEO-LoxP3 cassette was cloned into an Mlu...
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ورودعنوان ژورنال:
- Neuron
دوره 46 شماره
صفحات -
تاریخ انتشار 2005