Alpha B-crystallin is a small heat shock protein.

Abstract

Sequence similarity between aB-crystallin and small heat shock proteins (HSPs) has prompted us to investigate whether aB-crystallin expression is induced by heat shock. Indeed, accumulation of aB-crystallin was detected immunologically in NIH 3T3 cells after incubation at elevated temperatures and after addition of Cd2+ or sodium arsenite to these cells. Two-dimensional gel electrophoresis revealed identity between aB-crystallin from eye lenses and from heattreated fibroblasts. The promoter of the aB-crystallin gene was fused to the bacterial chloramphenicol acetyltransferase gene and was shown to confer heat inducibility on this reporter gene in transient transfection assays. A perfect heat shock element within the promoter region is likely to mediate this response. Small HSPs and aB-crystallin were shown to share the following two physical properties: (i) they form supramolecular structures with sedimentation values around 17 S and (ii) they are associated with the nucleus at high temperatures and are localized in the cytoplasm under normal conditions. We conclude that aB-crystallin has to be considered a member of the class of small HSPs.Heat shock and numerous other stress conditions lead to the rapid induction of several genes whose protein products are collectively called heat shock proteins (HSPs) (for recent reviews see refs. 1-3). The HSPs have been grouped into several classes on the basis of their size and sequence homology. Members of the class of small HSPs have molecular masses in the range 15-40 kDa. All analyzed organisms possess at least one small HSP gene. In mammals, birds, and yeast this class of HSPs is represented by a single member (4-9), whereas in Drosophila melanogaster and plants there appear to be multiple small HSPs (10, 11). Small HSPs aggregate to form characteristic ring-shaped structures called heat shock granules (4,(12)(13)(14)(15). These structures resemble prosomes or proteosomes but are distinct entities (16). Their biochemical function is unknown. Under heat shock conditions the small HSPs associate with the nucleus. Following a heat shock they slowly relocalize to the cytoplasm (17)(18)(19). It is still a matter of debate whether the small HSPs are actually transported into the nucleus at high temperatures or whether they are entrapped by the intermediate filaments, which, under heat shock conditions, collapse onto the nucleus (for a review see ref.3). The amino acid sequences of the small HSPs from different organisms are only poorly conserved. However, striking sequence similarities exist between vertebrate a-crystallins and small HSPs (5, 20-23). a-Crystallins were originally found in eye lenses, where they are among the most abundant proteins (24, 25). There exist two forms of a-crystallins, aA and aB, which are closely related (26). Considerable amounts of aB-crystallin, but not aAcrystallin, are present in many nonlenticular tissues (27-31). Moreover, aB-crystallin gene expression has been observed in various diseased cells, including astrocytes of patients s...

Small heat-shock proteins: important players in regulating cellular proteostasis

“…In this section we will discuss the role of c in the lens. 8 of the lens, Bc has a wide variety of metabolic and regulatory functions [62,63]; expression is induced by stress, for example by pH extremes, elevated temperature, chemical or heavy metal exposure, or hypertonic stress [64][65][66] and this confers both thermotolerance [67] and protection against oxidative stress to cells [68,69].…”

Puzzle of crystallin diversity in eye lenses

“…The aB-and, to a much more limited extent, ciA-crystallin genes are expressed in non-lens tissues (Bhat and Nagineni, 1989;Dubin et al, 1989;Iwaki et al, 1989;Kato et al, 1991). aB-crystallin is induced in non-lens cells by heat (Klemenz et al, 1991) and osmotic (Dasgupta et al, 1992) shock, and both CYA and aB can act as molecular chaperonins (Horwitz, 1992). aB-Crystallin is overexpressed in a number of transformed or diseased cells (see Piatigorsky, 1992 for references).…”

Immune and myodegenerative pathomechanisms in inclusion body myositis

“…The small heat shock protein α B crystallin is constitutively expressed in human skeletal muscle cells, binds misfolded proteins in order to avert their aggregation and its expression is sensitive to TNF‐ α ‐mediated induction 296, 297, 298. During AD pathology expression of α B crystallin is increased in CNS resident glial cells that are found in close spatial proximity to extracellular amyloid and neurofibrillary tangles 299.…”