A new feature of the stress response: increase in endocytosis mediated by Hsp70

The expression of heat shock proteins (HSP) is a conserved cellular response to a variety of stresses. These proteins have been found to refold denatured polypeptides and stabilize critical cellular processes. In this study, we introduce a new component of the stress response: the increase of receptor-mediated uptake of macromolecules from the external environment. We observed that endocytosis of transferrin, which is involved in the delivery of iron to the cell, was increased after stress induced by heat shock or after incubation with inhibitors of Hsp90 function. In both cases, the increase in endocytosis was reverted by inhibition of transcription, suggesting that gene expression is required. Transfection of cells with Hsp70 gene or inhibition of its expression by siRNA confirmed the role of this HSP in the increase of endocytosis. The mechanism for the enhancement of transferrin uptake was related to an accelerated internalization of the ligand-receptor complex as well as an increase in receptor recycling. These observations constitute a new paradigm for the cellular protection induced by HSP.