Interaction between TRPML1 and p62 in Regulating Autophagosome-Lysosome Fusion and Impeding Neuroaxonal Dystrophy in Alzheimer’s Disease

Figure 4

TRPML1 facilitates autophagosome-lysosome fusion through p62-mediated recruitment of dynein. (a) Changes of autolysosome formation in neurons detected by immunofluorescence staining. (b) Nuclear expression of BDNF in mouse hippocampal neurons identified by immunofluorescence staining. (c) Venn diagram flagging the intersection of TRPML1-related genes and AD-related genes in the GeneCards database and DisGeNet database. (d) Interaction network diagrams of the candidate genes, wherein the circle color from blue to orange represents the gene degree from small to large. (e) The interaction between TRPML1, p62, and dynein, confirmed by Co-IP. Neurons were treated with sh-p62 and/or oe-TRPML1 in the presence of Aβ1-42. (f) The extent of dynein phosphorylation in neurons. (g) Fusion of lysosomes and autophagosomes in neurons detected by immunofluorescence staining. Measurement data were described as the . One-way ANOVA was used for comparisons among multiple groups, followed by Tukey’s post hoc test. The cell experiment was repeated 3 times independently. vs. untreated HT22 cells; ^# vs. cells treated with oe-NC+Aβ1-42; ^{^} vs. cells treated with sh-NC+Aβ1-42 or oe-TRPML1+Aβ1-42; ^& vs. cells treated with oe-TRPML1+Aβ1-42 or ciliobrevin D+Aβ1-42.

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