Life Sciences & Biotechnology
Title : | Understanding the vital role of DnaJBs in maintaining neuronal protein homeostasis |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Smriti Priya, CSIR- Indian Institute Of Toxicology Research, Lucknow, Uttar Pradesh |
Timeline Start Year : | 2022 |
Timeline End Year : | 2025 |
Contact info : | smritipriya3@gmail.com |
Details
Executive Summary : | Molecular chaperones play a crucial role in maintaining protein homeostasis and the solubility of pathogenic proteins. The Hsp70-Hsp40 (DnaJ)-Hsp110 system is involved in refolding heat and stress denatured proteins under various conditions. Hsp70 collaborates with its co-chaperone Hsp40 (DnaJ), a J domain protein, to guide Hsp70 onto misfolded proteins and control the correlation between ATP consumption and substrate refolding by the Hsp70 chaperone system. The JB family proteins are associated with protein refolding and maintaining homeostasis. DnaJB proteins interact with the ATP-dependent Hsp70/110 (HSPA/HSPH) or Hsc70 refolding machinery. They are responsible for substrate specificity of Hsp70/110 and help transport and present misfolded proteins for refolding. The role of DnaJB proteins becomes intriguing under protein aggregation disorders, where failure of chaperone machinery leads to toxic protein accumulation and the collapse of protein homeostasis. Recent experimental evidence suggests a wider role of DnaJBs in maintaining neuronal protein homeostasis under proteotoxic stress conditions. However, comprehensive study on the functions of DnaJBs under cellular conditions is still unexplored. The "more than a co-chaperone" functions of DnaJBs in cellular conditions need to be addressed for their response to proteotoxic stress, modulating expression, and interaction partners. Studying DnaJBs' responses in different stress conditions would help to understand their cellular mechanisms and their functions in maintaining neuronal protein homeostasis and related diseases. |
Total Budget (INR): | 45,05,328 |
Organizations involved