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bioRxiv · 10.1101/2022.10.16.512122

Mrj an Hsp40 family chaperone regulates oligomerization of Orb2 and long-term memory

Desai, M.·Singh, H.·Deo, A.·Naik, J.·Bose, T.·Majumdar, A.
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Abstract

Orb2 the Drosophila homolog of Cytoplasmic polyadenylation element binding protein (CPEB) forms prion-like oligomers. These oligomers consist of Orb2A and Orb2B isoforms and their formation are dependent on the oligomerization of the Orb2A isoform. Drosophila with a mutation diminishing Orb2As prion-like oligomerization forms long-term memory but fails to maintain it over time. Since, this prion-like oligomerization of Orb2A plays a crucial role in the maintenance of memory, here we aim to find what regulates this oligomerization. In an immunoprecipitation-based screen, we identify interactors of Orb2A in the Hsp40 and Hsp70 families of proteins. Amongst these, we find an Hsp40 family protein Mrj as a regulator of the conversion of Orb2A to its prion-like form. Mrj interacts with Hsp70 proteins and acts as a chaperone by interfering with the aggregation of pathogenic Huntingtin. Unlike its mammalian homolog, we find Drosophila Mrj is neither an essential gene nor causes any gross neurodevelopmental defect. We observe a loss of Mrj results in a reduction in Orb2 oligomers. Further, the knockdown of Mrj in the mushroom body neurons results in a deficit in long-term memory. Our work implicates a chaperone Mrj in mechanisms of memory regulation through controlling the oligomerization of Orb2A and its association with the translating polysomes.

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Desai, M., Singh, H., Deo, A., Naik, J., Bose, T., Majumdar, A.. 2022-10-17. Mrj an Hsp40 family chaperone regulates oligomerization of Orb2 and long-term memory. https://doi.org/10.1101/2022.10.16.512122

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