Segregation of the receptor EphA7 from its tyrosine kinase-negative isoform on neurons in adult mouse brain.

The EphA7 gene encodes not only a typical receptor tyrosine kinase (TK+) but also an isoform lacking the tyrosine kinase domain (TK-). We have made antibodies to localise EphA7 TK+ and TK- isoforms in mouse brain. The TK- isoform was not detectable prenatally, despite reported expression of the TK- mRNA in the embryo. However, both TK+ and TK- isoforms showed striking distributions in adult brain. TK+ receptor immunoreactivity was strong in neuropil throughout most of the telencephalon, probably on fine arborisations from neurons which expressed EphA7 during development (in cerebral cortex, hippocampus, and striatum). In contrast, TK- receptor immunoreactivity was conspicuous on cell bodies and proximal dendrites of a limited number of neuronal types, some of which carried EphA7 TK+ receptor on their axons. This suggests that the TK- receptor, acting as a dominant negative antagonist, may ensure that the TK+ receptor only responds to signals encountered by the growing extremities of axons or dendrites.