TY  - JOUR
A1  - Donlin-Asp, Paul G.
A1  - Polisseni, Claudio
A1  - Klimek, Robin
A1  - Heckel, Alexander
A1  - Schuman, Erin M.
T1  - Differential regulation of local mRNA dynamics and translation following long-term potentiation and depression
T2  - Proceedings of the National Academy of Sciences of the United States of America
N2  - 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.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/74805
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-748056
SN  - 1091-6490
VL  - 118
IS  - 13,  e2017578118
PB  - Academy of Sciences of the United States of America
CY  - Washington, DC
ER  -