There's more than one way to skin a chimaerin

Abstract

In two manuscripts published in Neuron (Beg et al. and Wegmeyer et al.) and one published in Cell (Iwasato et al.), investigators have found that a particular GAP, alpha-chimaerin, is required in vivo for ephrinB3/EphA4-dependent motor circuit formation.

Figure 1. Model for α2-Chimaerin Activity in EphrinB3/EphA4 Forward Signaling

(A) EphrinB3 mediated axon guidance via EphA4 and α2-chimaerin in axonal process of cortical projection neurons. (B) EphrinB3 binds to EphA4. α2-Chimaerin binds to EphA4, and, in the presence of ephrinB3, its RAC-inactivating activity is increased. Chimaerin’s RAC-inactivation activity is also modulated with Nck2. EphA4s interact with RhoGEFs that may participate in other aspects of growth cone guidance. (C) Loss of ephrinB3, EphA4, or α-chimaerin leads to defects in gait resulting from axonal projection defects. Interestingly, only defects in guidance due to ephrinB3/EphA4 forward signaling are phenocopied by the loss of α-chimaerin.