Molecular chaperones, including the heat-shock proteins (Hsps), are a ubiquitous feature of cells in which these proteins cope with stress-induced denaturation of other proteins. Hsps have received the most attention in model organisms undergoing experimental stress in the laboratory, and the function of Hsps at the molecular and cellular level is becoming well understood in this context. A complementary focus is now emerging on the Hsps of both model and nonmodel organisms undergoing stress in nature, on the roles of Hsps in the stress physiology of whole multicellular eukaryotes and the tissues and organs they comprise, and on the ecological and evolutionary correlates of variation in Hsps and the genes that encode them. This focus discloses that (a) expression of Hsps can occur in nature, (b) all species have hsp genes but they vary in the patterns of their expression, (c) Hsp expression can be correlated with resistance to stress, and (d) species' thresholds for Hsp expression are correlated with levels of stress that they naturally undergo. These conclusions are now well established and may require little additional confirmation; many significant questions remain unanswered concerning both the mechanisms of Hsp-mediated stress tolerance at the organismal level and the evolutionary mechanisms that have diversified the hsp genes.

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Heat-shock proteins, molecular chaperones, and the stress response: evolutionary and ecological physiology

T URNOVER OF AB ERR ANT PROT EINS IN E. COLI . . . . . . . . . . . . . . . . . 445 The Lon Protease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 446 DnaK. DnaJ. GrpE. GroEL and GroES . . . . . . . . . . . . . . . . . . . . . . . . . . 447 The Clp Protease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 448 The DegP Protease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 452

The Function of Heat-Shock Proteins in Stress Tolerance: Degradation and Reactivation of Damaged Proteins

SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin-1

A novel kinase cascade triggered by stress and heat shock that stimulates MAPKAP kinase-2 and phosphorylation of the small heat shock proteins.

HSP70; CHARACTERISTICS AND FUNCTION S 582 HSP70 Diversity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . 582 Cytop lasmic HSP70 Genes and Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . .. 583 Cytoplasmic HSP70 Functions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . 586 HSP70 in the Endoplasmic Reticulum . . . . .. . . ..... . . .... . . . . . . . . ... . 588 Mitochondrial and Chloroplast HSP70s . . . .. . .. . . . . . . . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 588 H SP60 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 590 Mitochondrial HSP60 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 590 Chloroplast Chaperonin 60 . . . . . . . .... . . . . . .. . . . ....... ........ . ......... . ....... . . . . .. . . . ...... 591 LMW HSPs . . . . . . . . " . . ... .... ,... ....... . . . ........ . ...... . ...... 593 The LMW HSP Gene Supeifamily . . . . . . . . .. . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . .. . . . . . . . . . . 593 LMW HSP Structure . . . . . . . . . . . . . . . . . . . . . . . . . , .... , , 597 P lastid LMW HSPs . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . , ..... .... , 599 Endomembrane LMW HSPs . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . 601 LMW HSP Function . .. . . . .. . . . . . . .... . . . . . .... . . . .. . . . . . . . . . . . . . . . . . . . ... . . . . . . . .... . . . . . . . . . . . . 602 OTHER H SPs . . 604 HSP90 and HSPlJO. . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . 604 Ubiquitin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . , ... ,......... 605 Additional Heat-Regulated Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . 606 RELEV ANCE OF HSPS TO PLANT G ROWTH AND DEVELOPMENT 607 Expression of HSPs in the Natural Environment . . .. . . . . . . . ..... . . . . . .. . . . . . . . . . . ....... .. . 607 HSP Expression During Development 608 Role of HSPs in Thermotolerance . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . .. . . . . . . . . . 609 SUMMARY AND FUTURE PROSPECTS....... ....... ..... . .... .. . .. ....... ..... 611

The Roles of Heat Shock Proteins in Plants

Heat shock induces in cells the synthesis of specific proteins called heat shock proteins (HSPs) and a transient state of thermotolerance. The putative role of one of the HSPs, HSP27, as a protective molecule during thermal stress has been directly assessed by measuring the resistance to hyperthermia of Chinese hamster and mouse cells transfected with the human HSP27 gene contained in plasmid pHS2711. One- and two-dimensional gel electrophoresis of [3H]leucine- and [32P]orthophosphate-labeled proteins, coupled with immunological analysis using Ha27Ab and Hu27Ab, two rabbit antisera that specifically recognize the hamster and the human HSP27 protein respectively, were used to monitor expression and inducibility of the transfected and endogenous proteins. The human HSP27 gene cloned in pHS2711 is constitutively expressed in rodent cells, resulting in accumulation of the human HSP27 and all phosphorylated derivatives. No modification of the basal or heat-induced expression of endogenous HSPs is detected. The presence of additional HSP27 protein provides immediate protection against heat shock administered 48 h after transfection and confers a permanent thermoresistant phenotype to stable transfectant Chinese hamster and mouse cell lines. Mild heat treatment of the transfected cells results in an induction of the full complement of the endogenous heat shock proteins and a small increase in thermoresistance, but the level attained did not surpass that of heat-induced thermotolerant control cells. These results indicate that elevated levels of HSP27 is sufficient to give protection from thermal killing. It is concluded that HSP27 plays a major role in the increased thermal resistance acquired by cells after exposure to HSP inducers.

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Heat shock resistance conferred by expression of the human HSP27 gene in rodent cells.

Phosphorylation of heat shock protein 27 (HSP27) can modulate actinfilament dynamics in response to growth factors. During heat shock, HSP27 is phosphorylated at the same sites and by the same protein kinase as during mitogenic stimulation. This suggests that the same function of the protein may be activated during growth factor stimulation and the stress response. To determine the role of HSP27 phosphorylation in the heat shock response, several stable Chinese hamster cell lines that constitutively express various levels of the wild-type HSP27 (HU27 cells)oranonphosphorylatableformofhumanHSP27(HU27pm3cells)weredeveloped.IncontrasttoHU27cells, whichshowedincreasedsurvivalafterheatshock,HU27pm3cellsshowedonlyslightlyenhancedsurvival.Evidence is presented that stabilization of microfilaments is a major target of the protective function of HSP27. In the HU27pm3 cells, the microfilaments were thermosensitized compared with those in the control cells, whereas wild-typeHSP27causedanincreasedstabilityofthesestructuresinHU27cells.HU27butnotHU27pm3cellswere highly resistant to cytochalasin D treatment compared with control cells. Moreover, in cells treated with cytochalasin D, wild-type HSP27 but not the phosphorylated form of HSP27 accelerated the reappearance of actin filaments. The mutations in human HSP27 had no effect on heat shock-induced change in solubility and cellular localizationoftheprotein,indicatingthatphosphorylationwasnotinvolvedintheseprocesses.However,induction ofHSP27phosphorylationbystressingagentsormitogenscausedareductioninthemultimericsizeofthewild-type protein, an effect which was not observed with the mutant protein. We propose that early during stress, phosphorylation-induced conformational changes in the HSP27 oligomers regulate the activity of the protein at the level of microfilamentdynamics,resultinginbothenhancedstabilityandacceleratedrecoveryofthefilaments.Thelevelof protectionprovidedbyHSP27duringheatshockmaythusrepresentthecontributionofbettermaintenanceofactin filament integrity to overall cell survival.

Modulation of cellular thermoresistance and actin filament stability accompanies phosphorylation-induced changes in the oligomeric structure of heat shock protein 27.

Modulation of actin microfilament dynamics and fluid phase pinocytosis by phosphorylation of heat shock protein 27

Human HSP27 is phosphorylated at serines 78 and 82 by heat shock and mitogen-activated kinases that recognize the same amino acid motif as S6 kinase II.

E Hickey

Papers

Heat shock resistance conferred by expression of the human HSP27 gene in rodent cells.

Modulation of cellular thermoresistance and actin filament stability accompanies phosphorylation-induced changes in the oligomeric structure of heat shock protein 27.

Modulation of actin microfilament dynamics and fluid phase pinocytosis by phosphorylation of heat shock protein 27

Human HSP27 is phosphorylated at serines 78 and 82 by heat shock and mitogen-activated kinases that recognize the same amino acid motif as S6 kinase II.