A member of FK506 binding proteins family participates in the regulation of the autophagic pathway.

WAPPNER, P; MELANI, M; AGUILERA MO; COLOMBO MI

Santiago

Workshop; Autophagy: Physiological and Pathological Roles; 2016

ICGEB

Autophagy is a process in which a double membrane vesicle sequesters cytoplasmic material destined to degradation. Initially, autophagosome formation requires membrane remodeling to generate a vesicle which subsequently matures by fusion with other compartments. FKBP38 is one of the members of the FK506 binding proteins which play a role in some critical cellular functions such as protein trafficking and folding. FKBP38 forms a complex with Bcl2 and regulates the localization of this anti-apoptotic protein which also has a critical role in autophagy by interacting with Beclin 1. We have demonstrated that overexpression of FKBP38 stimulates the pathway whereas knock down of the protein leads to inhibition of autophagy. The participation of FKBP38 seems to be at an early step of the autophagic pathway because the protein colocalizes with Beclin 1 and Atg14, members of the PI3K complex, but not with LC3, a marker of later events in autophagosome formation. Surprisingly, starvation increased the colocalization between FKBP38 and markers of the endoplasmic reticulum and mitochondria, organelles that are the places where PI3K is recruited to initiate the membrane deformation.Taken together, our data indicate that FKBP38 regulates the autophagic pathway modulating early stages of autophagosome formation.