Differential regulation of local mRNA dynamics and translation following long-term potentiation and depression

  • Decades of work have demonstrated that mRNAs are localized and translated within neuronal dendrites and axons to provide proteins for remodeling and maintaining growth cones or synapses. It remains unknown, however, whether specific forms of plasticity differentially regulate the dynamics and translation of individual mRNA species. To address these issues, we targeted three individual synaptically-localized mRNAs, CamkIIa, Beta actin, Psd95, and used molecular beacons to track endogenous mRNA movements and reporters and Crispr-Cas9 gene editing to track their translation. We found widespread alterations in mRNA behavior during two forms of synaptic plasticity, long-term potentiation (LTP) and depression (LTD). Changes in mRNA dynamics following plasticity resulted in an enrichment of mRNA in the vicinity of dendritic spines. Both the reporters and tagging of endogenous proteins revealed the transcript-specific stimulation of protein synthesis following LTP or LTD. The plasticity-induced enrichment of mRNA near synapses could be uncoupled from its translational status. The enrichment of mRNA in the proximity of spines allows for localized signaling pathways to decode plasticity milieus and stimulate a specific translational profile, resulting in a customized remodeling of the synaptic proteome.

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Metadaten
Author:Paul G. Donlin-AspORCiD, Claudio Polisseni, Robin KlimekGND, Alexander HeckelORCiDGND, Erin M. SchumanORCiDGND
URN:urn:nbn:de:hebis:30:3-727881
DOI:https://doi.org/10.1101/2020.07.08.192369
Parent Title (English):bioRxiv
Document Type:Preprint
Language:English
Date of Publication (online):2020/07/09
Date of first Publication:2020/07/09
Publishing Institution:Universit├Ątsbibliothek Johann Christian Senckenberg
Release Date:2023/09/08
Issue:2020.07.08.192369
Page Number:47
HeBIS-PPN:512115125
Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Angeschlossene und kooperierende Institutionen / MPI f├╝r Hirnforschung
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universit├Ątspublikationen
Licence (German):License LogoCreative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International