MSc Exit Seminar- Aditi Aggarwal

Effect of thermal stress on the intracellular localization of constitutively expressed heat shock protein HSPA8 (Hsc70) in differentiated and undifferentiated cultured human neuronal cells

Heat shock protein HSPA8 (Hsc70) is a constitutively expressed member of the Hsp70 multigene family that is abundantly expressed in neuronal cells. Previous studies in our laboratory suggest that HSPA8 may play an important role in neuronal pre-protection against cellular stress. This thesis highlights the importance of HSPA8 and its role as a fast responder to cellular stress in differentiated human SH-SY5Y neuronal cells. The effect of thermal stress on the intracellular localization of HSPA8 is compared in differentiated and undifferentiated neuronal cells. HSPA8 rapidly translocated into the nuclei of differentiated neuronal cells after heat shock and co-localized at transcription sites with DNAJB1 (Hsp40) and HSPH1 (Hsp105α) components of the protein disaggregation/ refolding machine. The rapid targeting and assembly of an HSPA8 based disaggregation/ refolding machine acts as a nuclear protective mechanism in differentiated neurons without the time lag needed to induce stress-inducible Hsp70.

Supervisor:  Prof. Ian Brown