Fig. 7. The region around the second NPXY domain in LRP regulates APP processing. (A) Schematic illustration of two LRP-CT deletion constructs, LRP-CTΔ1 (lacking amino acids 4469–4484) or LRP-CTΔ2 (lacking amino acids 4486–4507). (B) Expression of LRP-CTΔ1 and LRP-CTΔ2 in LRP–/– cells is comparable to the endogenous level of LRP as seen by immunoblotting with LRP antibody 1704 (upper panel). The reduction in the levels of APP-CTFs in LRP–/– cells is restored by expression of the LRP-CTΔ1 but not the LRP-CTΔ2 construct. (C) Consistent with the results shown in (B), APPs secretion was restored to control LRP+/– levels only in the LRP-CTΔ1-transfected cell line but not in the LRP-CTΔ2 cell line. (D) LRP-CTΔNPVY (lacking amino acids 4504–4507), LRP-CTΔYATL (lacking amino acids 4507–4510) and LRP-CT (Y4507A) were expressed in LRP-deficient CHO 13-5-1 cells together with APP695 [see (A) for schematic]. Similarly to LRP-CTΔ2, expression of neither LRP-CTΔNPVY (top panel), LRP-CTΔYATL (top panel) nor LRP-CT (Y4507A) (bottom panel) was able to restore the reduction in APP-CTF levels or the increase in APPs to that seen in control K1 cells. In contrast, the expression of LRP-CT restored the deficiencies in APP processing in LRP–/– CHO 13-5-1 cells to control levels.