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Specialized Ribosomes for Neuronal Protein Synthesis

Specialized Ribosomes for Neuronal Protein Synthesis

Objective

The ability of the nervous system to respond adaptively relies on modifications to existing proteins as well as changes in gene transcription and mRNA translation. It is now clear that synapses possess the capacity for local protein synthesis, owing to the localization of ribosomes and mRNAs within dendrites. There is emerging interest in the possibility that ribosomes, as cellular machines, are not as static as typically assumed- and may be heterogeneous in composition and specialized for particular functions and cellular compartments. Intriguingly, several studies have noted the presence of ribosomal protein mRNAs in the dendrites and axons, raising the possibility that locally synthesized ribosomal proteins might serve to modify the local ribosome population. Amongst the players in protein synthesis, many signaling proteins, RNA-binding proteins, and most translation factors have been considered as potential regulatory hubs. The ribosomes, thus far, have not been considered. Here we propose to discover the nature and diversity of ribosomes present in neurons, their dendrites and their synapses in the rodent brain. Using a combination of RNA-sequencing, Mass Spectrometry, Fluorescence In situ Hybridization, and new labelling approaches to visualize nascent proteins, we will determine whether neuronal ribosomes are heterogeneous and specialized in different subcellular compartments. The proposed experiments will determine the relationship between the ribosome composition and the neuronal mRNAs that undergo translation. We will also examine how plasticity sculpts the ribosome population to regulate the changes in the proteome that are dynamically regulated by ongoing synaptic events and plasticity.
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Host institution

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV

Address

Hofgartenstrasse 8
80539 Munich

Germany

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 2 348 483

Beneficiaries (1)

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MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV

Germany

EU Contribution

€ 2 348 483

Project information

Grant agreement ID: 743216

Status

Ongoing project

  • Start date

    1 August 2017

  • End date

    31 July 2022

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 2 348 483

  • EU contribution

    € 2 348 483

Hosted by:

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV

Germany