The family of mammalian small heat shock proteins (HSPBs): Implications in protein deposit diseases and motor neuropathies

Boncoraglio, Alessandra; Minoia, Melania; Carra, Serena

doi:10.1016/j.biocel.2012.03.011

Cited by 73 publications

(65 citation statements)

References 149 publications

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“…rstb.royalsocietypublishing.org Phil Trans R Soc B 368: 20110409 spinal cord, sciatic nerve [1 -3] high [4] high [4] UP after hypoxic stress (in neonatal hippocampus) [39,40] n.a.…”

Section: Introductionmentioning

confidence: 99%

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Different anti-aggregation and pro-degradative functions of the members of the mammalian sHSP family in neurological disorders

Carra

Rusmini

Crippa

et al. 2013

Phil. Trans. R. Soc. B

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The family of the mammalian small heat-shock proteins consists of 10 members (sHSPs/HSPBs: HSPB1–HSPB10) that all share a highly conserved C-terminal alpha-crystallin domain, important for the modulation of both their structural and functional properties. HSPB proteins are biochemically classified as molecular chaperones and participate in protein quality control, preventing the aggregation of unfolded or misfolded proteins and/or assisting in their degradation. Thus, several members of the HSPB family have been suggested to be protective in a number of neurodegenerative and neuromuscular diseases that are characterized by protein misfolding. However, the pro-refolding, anti-aggregation or pro-degradative properties of the various members of the HSPB family differ largely, thereby influencing their efficacy and protective functions. Such diversity depends on several factors, including biochemical and physical properties of the unfolded/misfolded client, the expression levels and the subcellular localization of both the chaperone and the client proteins. Furthermore, although some HSPB members are inefficient at inhibiting protein aggregation, they can still exert neuroprotective effects by other, as yet unidentified, manners; e.g. by maintaining the proper cellular redox state or/and by preventing the activation of the apoptotic cascade. Here, we will focus our attention on how the differences in the activities of the HSPB proteins can influence neurodegenerative and neuromuscular disorders characterized by accumulation of aggregate-prone proteins. Understanding their mechanism of action may allow us to target a specific member in a specific cell type/disease for therapeutic purposes.

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“…rstb.royalsocietypublishing.org Phil Trans R Soc B 368: 20110409 spinal cord, sciatic nerve [1 -3] high [4] high [4] UP after hypoxic stress (in neonatal hippocampus) [39,40] n.a.…”

Section: Introductionmentioning

confidence: 99%

“…maintaining myofibrillar integrity [42] HSPB8 (Hsp22, H11, E2IG1) low in: cortex, cerebellum, striatum, hippocampus, spinal cord, sciatic nerve. low/moderate in motoneurons [1][2][3]43] high [4] high [4] n.a. n.a.…”

Section: Introductionmentioning

confidence: 99%

Different anti-aggregation and pro-degradative functions of the members of the mammalian sHSP family in neurological disorders

Carra

Rusmini

Crippa

et al. 2013

Phil. Trans. R. Soc. B

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“…It should also be emphasized that the endogenous expression levels of the various HSPB members substantially differ between cell types (11)(12)(13) and that HEK293 cells normally only express substantial levels of HSPB1, with the other members being expressed at very low levels only (40). Given that some of the HSPB members also can form heterooligomers (11,12), this complicates interpretation of functional comparisons from studies in different cell lines. Over the last years, only a few comparative studies have been done in which the 10 HSPB members were directly compared for their activity toward various substrates within the same cell models systems.…”

Section: Discussionmentioning

confidence: 99%

“…HSPBs have been shown to prevent the aggregation of several aggregation-inducing proteins, their effectiveness seemingly depending on the substrate and physical properties of the aggregate it forms (11). When coexpressing the different HSPB members with PARK2 C289G (see Fig.…”

Section: Hspb1mentioning

confidence: 99%

HSPA1A-Independent Suppression of PARK2 C289G Protein Aggregation by Human Small Heat Shock Proteins

Minoia

Grit

Kampinga

2014

Molecular and Cellular Biology

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The C289G mutation of the parkin E3-ubiquitin protein ligase (PARK2) is associated with autosomal recessive juvenile onset Parkinson's disease and was found to be associated with protein aggregation. Members of the human small heat shock proteins (HSPBs) have been implicated in protein degradation and prevention of protein aggregation. In this study, we show that of the 10 HSPB members, individual overexpression of HSPB1, HSPB2, HSPB4, and HSPB7 suppresses PARK2 C289G-associated protein aggregation. Intriguingly, the protective actions of these HSPBs are not impaired upon inactivation of the ATP-dependent HSP70 chaperone machines. Depending on the HSPB member the protective actions involve either autophagic or proteasomal degradation pathways.

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“…These proteins participate in regulation of the redox state of the cell and cytoskeleton, in proliferation and apoptosis, as well as in proteostasis that prevents aggregation of improperly folded proteins (Arrigo 2007;Ciocca et al 2013;Boncoraglio et al 2012). The human genome contains 10 genes encoding sHsp differently expressed in practically all tissues (Garrido et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Structure and properties of chimeric small heat shock proteins containing yellow fluorescent protein attached to their C-terminal ends

Datskevich

Gusev

2014

Cell Stress and Chaperones

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Recombinant chimeras of small heat shock proteins (sHsp) HspB1, HspB5, and HspB6 containing enhanced yellow fluorescent protein (EYFP) attached to their C-terminal ends were constructed and purified. Some properties of these chimeras were compared with the corresponding properties of the same chimeras containing EYFP attached to the Nterminal end of sHsp. The C-terminal fluorescent chimeras of HspB1 and HspB5 tend to aggregate and form a heterogeneous mixture of oligomers. The apparent molecular weight of the largest C-terminal chimeric oligomers was higher than that of the corresponding N-terminal chimeras or of the wild-type proteins; however, both homooligomers of N-terminal chimeras and homooligomers of C-terminal chimeras contained fewer subunits than the wild-type HspB1 or HspB5. Both Nterminal and C-terminal chimeras of HspB6 form small oligomers with an apparent molecular weight of 73-84 kDa. The C-terminal chimeras exchange their subunits with homologous wild-type proteins. Heterooligomers formed by the wild-type HspB1 (or HspB5) and the C-terminal chimeras of HspB6 differ in size and composition from heterooligomers formed by the corresponding wild-type proteins. As a rule, the N-terminal chimeras possess similar or slightly higher chaperone-like activity than the corresponding wild-type proteins, whereas the C-terminal chimeras always have a lower chaperone-like activity than the wild-type proteins. It is concluded that attachment of EYFP to either N-terminal or Cterminal ends of sHsp affects their oligomeric structure, their ability to form heterooligomers, and their chaperone-like activity. Therefore, the data obtained with fluorescent chimeras of sHsp expressed in the cell should be interpreted with caution.

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The family of mammalian small heat shock proteins (HSPBs): Implications in protein deposit diseases and motor neuropathies

Cited by 73 publications

References 149 publications

Different anti-aggregation and pro-degradative functions of the members of the mammalian sHSP family in neurological disorders

Different anti-aggregation and pro-degradative functions of the members of the mammalian sHSP family in neurological disorders

HSPA1A-Independent Suppression of PARK2 C289G Protein Aggregation by Human Small Heat Shock Proteins

Structure and properties of chimeric small heat shock proteins containing yellow fluorescent protein attached to their C-terminal ends

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