Ligand preference of EphB2 receptor is selectively regulated by N-glycosylation.

ABSTRACT: The Eph receptors and their ephrin ligands play important roles in cell communication and neuron development. Eph interacts with ephrin in a complex manner. Here, we found ephrin-B2 instead of well-recorded ephrin-A5 specifically recognize and activate EphB2 receptor in primary cortical neurons. Domain-swapping and N/Q mutagenesis results show that the ectodomain of EphB2 and its N-glycosylation sites are critical for the ephrin binding selectivity. The N265, N336, N428, and N482Q mutant EphB2 cannot distinguish ephrin-B2 from ephrin-A5. Furthermore, the N-glycosylation sites in EphB2 are evolutionarily conserved and the N-glycan-directed binding strategy is commonly used in other Eph family members. A gain-of-function EphB6 mutant restores its ephrin-B2 binding ability. Finally, EphB2 is

SUBMITTER: Lyu C 

PROVIDER: S-EPMC12052844 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature