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Role of HSPB8 in the Proteostasis Network: From Protein Synthesis to Protein Degradation and Beyond

  • Chapter
The Big Book on Small Heat Shock Proteins

Part of the book series: Heat Shock Proteins ((HESP,volume 8))

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Abstract

Proper protein folding is crucial for protein stability and function; when folding fails, due to stress or genetic mutations, proteins may become toxic. Cells have evolved a complex protein quality control (PQC) system to protect against the toxicity exerted by aberrantly folded proteins, that may aggregate accumulating in various cellular compartments perturbing essential cellular activities, ultimately leading to cell and neuron death. The PQC comprises molecular chaperones, degradative systems (proteasome and autophagy) and components of the unfolded protein response. Prevention of protein aggregation, clearance of misfolded substrates and attenuation of translation, which decreases the amount of misfolding clients to levels manageable by the molecular chaperones, are all key steps for the maintenance of proteostasis and cell survival. In parallel, alterations of proteostasis may also (indirectly) influence RNA homeostasis; in fact, RNA-containing aggregates, known as stress granules, accumulate in cells with impaired PQC and autophagy colocalizing with proteinaceous aggregates in several neurodegenerative diseases. Among the different molecular chaperones, here we will focus on the small heat shock protein HSPB8, which is expressed in neurons in basal conditions and upregulated in response to misfolded protein accumulation. HSPB8 exerts protective functions in several models of protein conformation neurodegenerative diseases. The putative sites of action of HSPB8 that confer HSPB8 pro-survival and anti-aggregation functions are discussed, as well as its potential role at the cross-road between proteostasis and ribostasis.

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Abbreviations

AD:

Alzheimer’s disease

ALS:

Amyotrophic lateral sclerosis

ATX2:

Ataxin 2

eIF2α:

Eukaryotic initiation factor 2 on Ser51 of the α subunit

FTLD-U:

Frontotemporal lobar degeneration with ubiquitin-positive inclusions

FUS:

Fused in sarcoma

HD:

Huntington’s disease

hnRNPA1:

Heterogeneous nuclear ribonucleoprotein A1

HSP:

Heat shock protein

IBMPFD:

Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia

JNK:

c-Jun N-terminal kinase

KD:

Kennedy’s disease

LAMP2A:

Lysosome-associated membrane protein 2A

LC3:

Microtubule-associated protein 1A/1B-light chain 3

MKK7:

Mitogen-activated Protein Kinase Kinase 7

MSP:

Multisystem proteinopathy

NBR1:

Neighbor of BRCA1 gene 1

PD:

Parkinson’s disease

PERK:

Protein kinase RNA-like endoplasmic reticulum kinase

polyQ:

Polyglutamine

PQC:

Protein quality control

RACK1:

Receptor for Activated C Kinase 1

rhoA:

Ras homolog gene family member A

RNPs:

Ribonucleic proteins

ROCK1:

Rho-associated coiled-coil containing protein kinase 1

SCA3:

Spinocerebellar ataxia 3

SG:

Stress granule

SOD1:

Superoxide dismutase 1

SQSTM1:

Sequestosome 1

TDP-43:

TAR DNA-binding protein 43

TIA-1:

T-cell intracytoplasmic antigen

TRAF2:

TNF receptor-associated factor 2

UPS:

Ubiquitin proteasome system

VCP:

Valosin containing protein

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Acknowledgments

Serena Carra is grateful to MIUR (Rita Levi Montalcini Principal Research Fellowship). Serena Carra and Angelo Poletti are grateful to The AriSLA Foundation, Cariplo Foundation, AFM-Telethon France for support. Angelo Poletti is also graeful to Telethon, Italy, Regione Lombardia and the University of Milan for support.

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Authors and Affiliations

  1. Dipartimento di Scienze Farmacologiche e Biomolecolari (DiSFeB), Universita’ degli Studi di Milano, via Balzaretti 9, 20133, Milano, Italy

    Angelo Poletti

  2. Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze, Universita’ di Modena e Reggio Emilia, via G. Campi 287, 41125, Modena, Italy

    Serena Carra

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  1. Angelo Poletti
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  2. Serena Carra
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Correspondence to Serena Carra .

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  1. Department of Molecular Biology, Medical Biochemistry & Pathology Medical School Lab Cell & Developmental Genetics IBIS, Université Laval, Quebec, Québec, Canada

    Robert M. Tanguay

  2. Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut, USA

    Lawrence E. Hightower

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Poletti, A., Carra, S. (2015). Role of HSPB8 in the Proteostasis Network: From Protein Synthesis to Protein Degradation and Beyond. In: Tanguay, R., Hightower, L. (eds) The Big Book on Small Heat Shock Proteins. Heat Shock Proteins, vol 8. Springer, Cham. https://doi.org/10.1007/978-3-319-16077-1_21

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