Extracellular Hsp70: export and function.
The most conserved cellular response to stress is the expression of heat shock proteins (hsp). These proteins participate in the repair of cellular damage after the stress, which is necessary for a positive recovery and confers further protection from subsequent insults. Since these proteins are expressed in subcellular compartments, it was thought that their function during stress conditions was circumscribed to the intracellular environment. However, it is now well established that hsp can also be present outside cells, where they appear to display a function different than the well understood chaperone role. Extracellular hsp act as alert stress signals priming other cells, particularly of the immune system, to avoid the propagation of the insult and favoring resolution. A very pertinent question to ask is what is the mechanism for the export of these proteins into the extracellular environment, since they do not possess a secretory leading signal? Different mechanisms have been proposed, including translocation across the plasma membrane and release associated with lipid vesicles, an endolysosomal pathway, and the passive release after cell death by necrosis. Extracellular hsp appears to be in membrane-bound and membrane-free forms. They could be associated with substrate or free of client proteins. All of these variants of extracellular hsp suggest that their interactions with cells may be quite diverse, both in target cell-types and the activating signal pathways. This review addresses some of our current knowledge about the function and release of extracellular hsp, in particular the major inducible form, Hsp70.
University of California San Diego, 9500 Gilman Drive, #0739, La Jolla, CA 92093-0739, USA. ademaio@ucsd.edu.
Antonio
A
De Maio
D002450:Cell Communication; D002462:Cell Membrane / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D021381:Protein Transport
D018840:HSP70 Heat-Shock Proteins