Mrj is a chaperone of the Hsp40 family that regulates Orb2 oligomerization and long-term memory in Drosophila.

Autor: Desai M; National Centre for Cell Science, Savitribai Phule Pune University Campus, Pune, India., Hemant; National Centre for Cell Science, Savitribai Phule Pune University Campus, Pune, India., Deo A; Institute of Bioinformatics and Biotechnology (IBB), Savitribai Phule Pune University, Pune, India., Naik J; National Centre for Cell Science, Savitribai Phule Pune University Campus, Pune, India., Dhamale P; National Centre for Cell Science, Savitribai Phule Pune University Campus, Pune, India., Kshirsagar A; National Centre for Cell Science, Savitribai Phule Pune University Campus, Pune, India., Bose T; Institute of Bioinformatics and Biotechnology (IBB), Savitribai Phule Pune University, Pune, India., Majumdar A; National Centre for Cell Science, Savitribai Phule Pune University Campus, Pune, India.
Jazyk: angličtina
Zdroj: PLoS biology [PLoS Biol] 2024 Apr 22; Vol. 22 (4), pp. e3002585. Date of Electronic Publication: 2024 Apr 22 (Print Publication: 2024).
DOI: 10.1371/journal.pbio.3002585
Abstrakt: Orb2 the Drosophila homolog of cytoplasmic polyadenylation element binding (CPEB) protein forms prion-like oligomers. These oligomers consist of Orb2A and Orb2B isoforms and their formation is dependent on the oligomerization of the Orb2A isoform. Drosophila with a mutation diminishing Orb2A's 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. Among 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, Mrj knockout exhibits a deficit in long-term memory and our observations suggest Mrj is needed in mushroom body neurons for the regulation of 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 ribosomes.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Desai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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