Figure 6.
Figure 6. PSEN2 accumulates within axonal swellings in JIP3 KO neurons. (A and B) PSEN2, LAMP1, and MAP2 immunofluorescence shows that PSEN2 colocalizes with lysosomes in neuronal cell bodies, axons, and dendrites of both WT and KO neurons. Large accumulations of PSEN2 on lysosomes in axonal swellings are selectively observed in JIP3 KO neurons (arrows; images are representative of results from five independent cultures). Bars, 10 µm. (C and D) Magnified images showing PSEN2 (green) and LAMP1 (red) colocalization in both WT (C) and JIP3 KO (D) axons. Bars, 1 µm. All results obtained from DIV 10–12 neuronal cultures. (E) Quantification of endogenous mouse Aβ42 based on ELISA measurements (mean ± SD) from n = 5 independent WT and KO cultures (***, P < 0.001, unpaired t test). (F) Schematic diagram summarizing that axonal lysosome accumulations in the JIP3 KO neurons are accompanied by the local buildup of APP, BACE1, and PSEN2 and increased production of Aβ42.

PSEN2 accumulates within axonal swellings in JIP3 KO neurons. (A and B) PSEN2, LAMP1, and MAP2 immunofluorescence shows that PSEN2 colocalizes with lysosomes in neuronal cell bodies, axons, and dendrites of both WT and KO neurons. Large accumulations of PSEN2 on lysosomes in axonal swellings are selectively observed in JIP3 KO neurons (arrows; images are representative of results from five independent cultures). Bars, 10 µm. (C and D) Magnified images showing PSEN2 (green) and LAMP1 (red) colocalization in both WT (C) and JIP3 KO (D) axons. Bars, 1 µm. All results obtained from DIV 10–12 neuronal cultures. (E) Quantification of endogenous mouse Aβ42 based on ELISA measurements (mean ± SD) from n = 5 independent WT and KO cultures (***, P < 0.001, unpaired t test). (F) Schematic diagram summarizing that axonal lysosome accumulations in the JIP3 KO neurons are accompanied by the local buildup of APP, BACE1, and PSEN2 and increased production of Aβ42.

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