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

  • Decades of work have demonstrated that messenger RNAs (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 this, we targeted three individual synaptically localized mRNAs, CamkIIa, β-actin, Psd95, and used molecular beacons to track endogenous mRNA movements. We used reporters and CRISPR/Cas9 gene editing to track mRNA translation in cultured neurons. We found alterations in mRNA dynamic properties occurred during two forms of synaptic plasticity, long-term potentiation (cLTP) and depression (mGluR-LTD). Changes in mRNA dynamics following either form of 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 cLTP or mGluR-LTD. As such, 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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Author:Paul G. Donlin-AspORCiD, Claudio Polisseni, Robin KlimekGND, Alexander HeckelORCiDGND, Erin M. SchumanORCiDGND
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/33771924
Parent Title (English):Proceedings of the National Academy of Sciences of the United States of America
Publisher:Academy of Sciences of the United States of America
Place of publication:Washington, DC
Document Type:Article
Date of Publication (online):2021/03/26
Date of first Publication:2021/03/26
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/09/08
Issue:13, e2017578118
Article Number:e2017578118
Page Number:12
Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Angeschlossene und kooperierende Institutionen / MPI für 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
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International