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.
Vega
Virginia L
VL
UCSD Department of Surgery, University of California San Diego, 9500 Gilman Drive, 0739, La Jolla, CA 92093-0739, USA.
Charles
Wisler
W
De Maio
Antonio
A
D016227:Benzoquinones / Q000494:pharmacology; D015153:Blotting, Western; D004705:Endocytosis / Q000187:drug effects* / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D018869:Heat-Shock Response / Q000235:genetics / Q000502:physiology; D056945:Hep G2 Cells; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics / Q000502:physiology; D011990:Receptors, Transferrin / Q000378:metabolism; D013696:Temperature; D014168:Transferrin / Q000235:genetics / Q000378:metabolism
D016227:Benzoquinones; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D034741:RNA, Small Interfering; D011990:Receptors, Transferrin; D014168:Transferrin; C001277:geldanamycin