biostudies-literatureAlecki CALS Society of Canada (ALS Canada)NIMH NIH HHSNHGRI NIH HHSNCI NIH HHSNINDS NIH HHSU.S. Department of Health & Human Services | National Institutes of Health (NIH)Fonds de Recherche du Québec - Santé (Fonds de la recherche en sante du Quebec)Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)10796https://www.ebi.ac.uk/biostudies/studies/S-EPMC11685665biostudies-literatureUnknown15(1)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 Nature communicationsLocalized molecular chaperone synthesis maintains neuronal dendrite proteostasis.PMC11685665HG011864P30 CA008748HG0098892022-ALS Discovery GrantR01 HG004659U41 HG009889PJT-186141HG004659R01 HG011864R01 NS103172RF1 MH126719MH126719300232Hudson Translational Team GrantU24 HG009889Lynch JVerbrugghe MAlecki CXu JMSJacob-Tomas SYeo GWLe PVera MComaduran MFRizwan JBiswas JDurham HDWu TMinotti SfalseLocalized molecular chaperone synthesis maintains neuronal dendrite proteostasis.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 2024-01-01T00:00:00Z2024 Dec2026-06-02T07:28:03.351Z2025-04-05T17:01:11.283ZS-EPMC116856653973795210.1038/s41467-024-55055-7