Editors' ChoiceNeurobiology

Truncated Receptors Are More Attractive

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Science's STKE  14 Nov 2000:
Vol. 2000, Issue 58, pp. tw2
DOI: 10.1126/stke.2000.58.tw2

Ephrins (Ephs) are membrane-bound ligands that are typically thought to mediate axon repulsion. Holmberg, Clarke, and Frisén observed that in EphA5 null mice, there was a defect in neural tube closure, suggesting a role for EphA5 in neural adhesion, rather than repulsion. Analysis of the ephrin receptors (EphRs) expressed in the developing neural tube indicated that three splice variants of the EphR (EphA7-FL, full-length; EphA7-T1 and EphA7-T2, truncated versions) were expressed at similar times and in patterns similar to those of the EphA5 ligand. EphA7-FL is a receptor tyrosine kinase, whereas the two truncated versions lack the kinase domain. Coexpression of the FL and T1 forms in 293 cells converted an EphA5 repulsive signal into an adhesive signal. This is opposite to the repulsive effects of EphA5 on cells expressing EphA7-FL only. Furthermore, stimulation of tyrosine phosphorylation of the FL receptor by EphA5 binding was inhibited when EphA7-T1 was coexpressed, suggesting that the T1 form acts as an endogenous dominant negative version of the Eph receptor. Thus, regulated expression of alternative splice variants of EphRs appears to convert a repulsive signal into an attractive one.

Holmberg, J., Clarke, D.L., and Frisén, J. (2000) Regulation of repulsion versus adhesion by different splice forms of an Eph receptor. Nature 408: 203-206. [Online Journal]