Figure 9

Model of Reelin-EphB signaling crosstalk. (A) Oligomerized Reelin binds to the lipoprotein receptors ApoerER2 or VLDLR (orange) with its central fragment (Reelin repeats 3-6), whereas the amino-terminal domain (green) interacts with EphB2 (red). The composition and turnover of the Reelin-receptor supramolecular complex and thereby its signaling output are dynamically regulated, depending on the developmental stage, tissue expression and activity of additional molecules interacting with Reelin and its receptors, and the proteolytic cleavage of Reelin and its receptors by metalloproteases (arrowheads) and the intramembrane γ-secretase complex (arrows). (B) Model of how Reelin-induced ApoE receptor and Eph/ephrin-dependent signaling cascades may interact to regulate cellular behavior in responsive neurons. Reelin might activate different receptor systems individually or recruit them into larger macromolecular complexes, either in cis or in trans, which would differentially modulate the signaling output of its components. Abbreviations: SFK, Src family kinase; PTB: phosphotyrosine binding domain; NPXY, Asn-Pro-X-Tyr tetra-amino-acid motif; PI3K, phosphatidylinositol-3-kinase; ^*19, alternatively spliced exon 19 of ApoER2.