APP–BP1- and APP(V642I)-mediated changes in the morphology of early endosomes are dependent on the binding of APP–BP1 to APP but are independent of the neddylation pathway. Primary neurons expressing exogenous APP–BP1 or APP(V642I) were coinfected with either APP–BP1(145–251), the region to which APP binds, or Ubc12(C111S), a dominant-negative mutant in the neddylation pathway. Neurons were then fixed and stained with mouse anti-EEA1 (red) and rabbit anti-Rab5 (green). The right side of each image shows the merged image of EEA1 and Rab5, depicting early endosomes. The insets are enlarged images demonstrating discrete endosomes in single neurons. A, Coexpression of APP–BP1(145–251) with APP–BP1 or APP(V642I) in primary neurons blocks the increase in number and size of early endosomes seen in neurons expressing APP–BP1 or APP(V642I) alone. B, In contrast, coexpression of Ubc12(C111S) does not block the increase in number and size of early endosomes seen in neurons expressing APP–BP1 or APP(V642I) alone. Scale bar, 5 μm.