Relationship between annexin A7 and integrin beta 4 in autophagy

We recently found that both annexin A7 and integrin beta 4 were involved in autophagy of vascular endothelial cells. But, their relation is not clear. In this study, we addressed this question by using a small molecule ABO that promoted autophagy by targeting annexin A7. The results showed that knockdown of integrin beta 4 partly inhibited ABO-induced autophagy in vascular endothelial cells. Furthermore, in HEK293 cells that express integrin beta 4 too low to detect by western blot, ABO could not induce autophagy. If integrin beta 4 was overexpressed in HEK293 cells, ABO could evoke autophagy. On the other hand, knockdown of annexin A7 also blocked ABO-induced autophagy although the level of integrin beta 4 was elevated. Moreover, by co-immunoprecipitation, we identified the interaction of integrin beta 4 and annexin A7, and found that ABO could modulate the interaction, at the same time, the phosphorylation of Y-1494 in integrin beta 4 cytoplasmic domain was inhibited significantly in vitro and in vivo. Hence, by identifying the interaction between integrin beta 4 and annexin A7, we demonstrated that both annexin A7 and integrin beta 4 were essential for small molecule ABO-induced autophagy and targeting annexin A7 by ABO could modulate integrin beta 4 phosphorylation, while Y-1494 phosphorylation of integrin beta 4 may negatively regulate autophagy.