Eph Receptors and Ligands Comprise Two Major Specificity Subclasses and Are Reciprocally Compartmentalized during Embryogenesis

Abstract

We report that the many Eph-related receptor tyrosine kinases, and their numerous membrane-bound ligands, can each be grouped into only two major specificity subclasses. Receptors in a given subclass bind most members of a corresponding ligand subclass. The physiological relevance of these groupings is suggested by viewing the collective distributions of all members of a subclass. These composite distributions, in contrast with less informative patterns seen with individual members of the family, reveal that the developing embryo is subdivided into domains defined by reciprocal and apparently mutually exclusive expression of a receptor subclass and its corresponding ligands. Receptors seem to encounter their ligands only at the interface between these domains. This reciprocal compartmentalization implicates the Eph family in the formation of spatial boundaries that may help to organize the developing body plan.

Global DNA methylation profiling reveals silencing of a secreted form of Epha7 in mouse and human germinal center B-cell lymphomas

“…Accordingly, we found that recombinant soluble EphA7 blocked ephrinA4-induced EphA7-FL phosphorylation in vitro. Given its promiscuity for various ephrin-A ligands (Gale et al, 1996), it is intriguing to hypothesize that EphA7 secreted by lymphocytes might act as a decoy to block EphA receptor-ephrinA ligand clustering and activation. In this manner, soluble EphA7 could influence lymphocyte chemotaxis and trafficking by inhibiting Eph/ephrin interaction and signaling between adjacent lymphocytes or other neighboring cells (i.e., dendritic cells, macrophages or endothelium).…”

Axon guidance at the midline choice point

“…Eph receptors are divided into two subclasses: EphA receptors that preferentially interact with A-class ephrin ligands and EphB receptors that preferentially interact with B-class ephrin ligands. While both types of ephrins are associated with the cell surface, A-class ephrin ligands are tethered to the membrane through a glycosyl phosphatidylinositol (GPI) linkage, whereas B-class ephrin ligands possess transmembrane domains (see Gale et al, 1996;Flanagan and Vanderhaeghen, 1998 and references therein). The ability of B-class ephrins to mediate contact-dependent repulsion in a number of neural systems (see Flanagan and Vanderhaeghen, 1998;Holder and Klein, 1999;Wilkinson, 2000) makes them particularly well-suited to function as highly localized repellent guidance cues at the ventral midline.…”

Regeneration of lesioned corticospinal tract fibers in the adult rat spinal cord under experimental conditions

“…10,49,50 Infusions of some of these factors or local implantation of ®broblasts producing these factors from a transgene have been analysed in spinal cord lesions. 51,52 Enhanced sprouting and growth of axons were found.…”