Localized molecular chaperone synthesis maintains neuronal dendrite proteostasis

Célia Alecki, Javeria Rizwan, Phuong Le, Suleima Jacob-Tomas, Mario Fernandez Comaduran, Morgane Verbrugghe, Jia Ming Stella Xu, Sandra Minotti, James Lynch, Jeetayu Biswas, Tad Wu, Heather D. Durham, Gene W. Yeo and Maria Vera ()
Additional contact information
Célia Alecki: McGill University
Javeria Rizwan: McGill University
Phuong Le: University of California
Suleima Jacob-Tomas: McGill University
Mario Fernandez Comaduran: McGill University
Morgane Verbrugghe: McGill University
Jia Ming Stella Xu: McGill University
Sandra Minotti: McGill University
James Lynch: McGill University
Jeetayu Biswas: Memorial Sloan Kettering Cancer Center
Tad Wu: McGill University
Heather D. Durham: McGill University
Gene W. Yeo: University of California
Maria Vera: McGill University

Nature Communications, 2024, vol. 15, issue 1, 1-22

Abstract: Abstract Proteostasis is maintained through regulated protein synthesis and degradation and chaperone-assisted protein folding. However, this is challenging in neuronal projections because of their polarized morphology and constant synaptic proteome remodeling. Using high-resolution fluorescence microscopy, we discover that hippocampal and spinal cord motor neurons of mouse and human origin localize a subset of chaperone mRNAs to their dendrites and use microtubule-based transport to increase this asymmetric localization following proteotoxic stress. The most abundant dendritic chaperone mRNA encodes a constitutive heat shock protein 70 family member (HSPA8). Proteotoxic stress also enhances HSPA8 mRNA translation efficiency in dendrites. Stress-mediated HSPA8 mRNA localization to the dendrites is impaired by depleting fused in sarcoma—an amyotrophic lateral sclerosis-related protein—in cultured spinal cord mouse motor neurons or by expressing a pathogenic variant of heterogenous nuclear ribonucleoprotein A2/B1 in neurons derived from human induced pluripotent stem cells. These results reveal a neuronal stress response in which RNA-binding proteins increase the dendritic localization of HSPA8 mRNA to maintain proteostasis and prevent neurodegeneration.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-55055-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-55055-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-55055-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().