Affiliations: Department of Biological Sciences, Centre for the Neurobiology of Stress, University of Toronto Scarborough, Toronto, Ontario, Canada
Correspondence:
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Correspondence to: Dr. Ian R. Brown, Centre for the Neurobiology of Stress, Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, Ontario M1C 1A4, Canada. Tel.: +1 416-287-7413; E-mail: [email protected].
Abstract: HSPA6 (Hsp70B’) is an inducible member of the Hsp70 (HSPA) family of heat shock proteins that is present in the human genome and not found in mouse and rat. Hence it is lacking in current animal models of neurodegenerative diseases. To advance knowledge of the little studied HSPA6, differentiated human neuronal SH-SY5Y cells were treated with the proteotoxic stress-inducing agent MG132. A robust induction of HSPA6 was apparent which localized to the periphery of MG132-induced protein aggregates in the neuronal cytoplasm. Components of the protein disaggregation/refolding machine that co-operate with Hsp70 also targeted the periphery of cytoplasmic protein aggregates, including DNAJB1 (Hsp40–1), HSPH1 (Hsp105α), and HSPB1 (Hsp27). These data suggest that HSPA6 is involved in the response of human neuronal cells to proteotoxic stress that is a feature of neurodegenerative diseases which have been characterized as protein misfolding disorders. Constitutively expressed HSPA8 (Hsc70) also localized tothe periphery of cytoplasmic protein aggregates following the treatment of differentiated human neuronal cells with MG132. HSPA8 could provide a rapid response to proteotoxic stress in neuronal cells, circumventing the time required to upregulate inducible Hsps.
Keywords: Heat shock protein (Hsp), HSPA6 (Hsp70B’), HSPA8 (Hsc70), human neuronal SH-SY5Y cells, MG132, protein disaggregation/refolding machine, proteotoxic stress
