The Pafah1b Complex Interacts with the Reelin Receptor VLDLR (original) (raw)
Figure 8
Integrated model of Reelin and Lis1 signaling. Reelin binds to VLDLR and ApoER2 and causes src-family kinase (SFK) activation and Dab1 phosphorylation. Dab1 binds to the NPxY motif of both, VLDLR and ApoER2. Upon Reelin stimulation, phosphoDab1 (P-Dab1) interacts with Lis1 and with other signal transduction molecules (grey circles). Lis1 also binds the catalytic subunits of the Pafah1b complex (α1 and α2) as well as components of the cytoplasmic dynein complex (yellow square). α1 and α2 also bind VLDLR at the NPxYL motif and compete with Dab1 for receptor occupancy. These subunits do not recognize the NPxYR motif of ApoER2. A unique domain of ApoER2 enables unique interactions with synaptic and trafficking proteins (white octagons). The binding of catalytic Pafah1b subunits to VLDLR may displace P-Dab1 and promote its interaction with Lis1. Signaling molecules downstream of Lis1 and Dab1 affect cytoskeleton dynamics by acting on microtubules (thick lines) or actin filaments (thin lines), thereby controlling neuronal migration and layer formation.