Selective release from cultured mammalian cells of heat-shock (stress) proteins that resemble glia-axon transfer proteins.
Cultured rat embryo cells were stimulated to rapidly release a small group of proteins that included several heat-shock proteins (hsp110, hsp71, hscp73) and nonmuscle actin. The extracellular proteins were analyzed by two-dimensional polyacrylamide gel electrophoresis. Heat-shocked cells released the same set of proteins as control cells with the addition of the stress-inducible hsp110 and hsp71. Release of these proteins was not blocked by either monensin or colchicine, inhibitors of the common secretory pathway. A small amount of the glucose-regulated protein grp78 was externalized by this pathway. The extracellular accumulation of these proteins was inhibited after they were synthesized in the presence of the lysine analogue aminoethyl cysteine. It is likely that the analogue-substituted proteins were misfolded and could not be released from cells, supporting our conclusion that a selective release mechanism is involved. Remarkably, actin and the squid heat-shock proteins homologous to rat hsp71 and hsp110 are also among a select group of proteins transferred from glial cells to the squid giant axon, where they have been implicated in neuronal stress responses (Tytell et al.: Brain Res., 363:161-164, 1986). Based in part on the similarities between these two sets of proteins, we hypothesized that these proteins were released from labile cortical regions of animal cells in response to perturbations of homeostasis in cells as evolutionarily distinct as cultured rat embryo cells and squid glial cells.
Hightower
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LE
Department of Molecular and Cell Biology, University of Connecticut, Storrs 06268.
Guidon
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PT
D000199:Actins / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism*; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D006360:Heat-Shock Proteins / Q000032:analysis / Q000378:metabolism*; D007700:Kinetics; D008985:Monensin / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism*; D051381:Rats
D000199:Actins; D006360:Heat-Shock Proteins; D009419:Nerve Tissue Proteins; D008985:Monensin; D003078:Colchicine