Role of FKBP in the Initiation of Autophagy

초록

FK506 binding protein 51 (FKBP51, also known as FKBP5) belongs to a family of immunophilins that binds to the immunosuppressants FK506 and rapamycin. The scaffolding activity of FKBP5 enables it to play a modulatory role in the immune response, tumorigenesis, cell death and the stress hormone axis. It has been recently reported that FKBP5 is involved in autophagy, an intracellular degradation system necessary for the maintenance of cellular homeostasis. However, the molecular mechanism for how FKBP5 regulates autophagy remains unclear. Here, we show that autophagic flux was impaired by a loss of FKBP5 both in the feeding and starvation conditions. The autophagic defect of the FKBP5-deficient cells was accompanied by a decrease in the levels of VPS34 complex proteins that are required for autophagy initiation. Also, we revealed that FKBP5 physically interacts with the complex. These findings suggest that FKBP5 may facilitate the autophagic process by stabilizing the autophagy initiation complex.