Overexpression of Lysosomal-Associated Protein Transmembrane 5 (LAPTM5) Deceases Autophagy Activity Via Reducing the Lysosomal pH Value

Abstract

Lysosomal-associated protein transmembrane 5 (LAPTM5) encodes a transmembrane protein in lysosomal, which is specifically expressed in hematopoietic system. Autophagy, a lysosomal degradation pathway, is now emerging as an importance prosurvival or prodeath factor in response to some chemotherapy. In our previously study, we found the expression of LAPTM5 is closely related with acute lymphocytic leukemia, but exactly role of this gene in acute leukemia(AL) was unknown. To investigate the association of LAPTM5 with autophagy, we overexpressed LAPTM5 in K562 cells, and the results showed LAPTM5 significantly decreased autophagy activity, which measured by testing the conversion of LC3-I to LC3-II and LC3-II dots using western blotting and imaging flow cytometry, respectively(Figure 1 and 2). Moreover, PCR array was performed to detect the changes of 92 genes regulating autophagic activity in LAPTM5 overexpressed cells, and 73 autophagy-related genes were found downregulated. Finally, the overexpression of LAPTM5 significantly reduced the pH value in lysosomal, which was very essential for autophagy-mediated degradation activity (Figure 3). Taken together, these results suggest that LAPTM5 decreased autophagy activity though downregulation of pH value in lysosomal. Therefore, LAPTM5 might represent a potential target modulating autophagy activity to increase sensitivity to chemotherapy in treatment of AL. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.