scholarly journals Monosomes actively translate synaptic mRNAs in neuronal processes

Science ◽  
2020 ◽  
Vol 367 (6477) ◽  
pp. eaay4991 ◽  
Author(s):  
Anne Biever ◽  
Caspar Glock ◽  
Georgi Tushev ◽  
Elena Ciirdaeva ◽  
Tamas Dalmay ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Active Sites ◽  
Synaptic Proteins ◽  
Messenger Rnas ◽  
Local Protein Synthesis ◽  
Relative Paucity ◽  
Polysome Profiling ◽  
Neuronal Processes ◽  
Ribosome Footprinting ◽  
Local Protein

To accommodate their complex morphology, neurons localize messenger RNAs (mRNAs) and ribosomes near synapses to produce proteins locally. However, a relative paucity of polysomes (considered the active sites of translation) detected in electron micrographs of neuronal processes has suggested a limited capacity for local protein synthesis. In this study, we used polysome profiling together with ribosome footprinting of microdissected rodent synaptic regions to reveal a surprisingly high number of dendritic and/or axonal transcripts preferentially associated with monosomes (single ribosomes). Furthermore, the neuronal monosomes were in the process of active protein synthesis. Most mRNAs showed a similar translational status in the cell bodies and neurites, but some transcripts exhibited differential ribosome occupancy in the compartments. Monosome-preferring transcripts often encoded high-abundance synaptic proteins. Thus, monosome translation contributes to the local neuronal proteome.

scholarly journals Monosomes actively translate synaptic mRNAs in neuronal processes

2019 ◽  
Author(s):  
Anne Biever ◽  
Caspar Glock ◽  
Georgi Tushev ◽  
Elena Ciirdaeva ◽  
Julian D. Langer ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Active Sites ◽  
Synaptic Proteins ◽  
Local Protein Synthesis ◽  
Relative Paucity ◽  
Large Size ◽  
Polysome Profiling ◽  
Neuronal Processes ◽  
Ribosome Footprinting ◽  
Local Protein

AbstractIn order to deal with their huge volume and complex morphology, neurons localize mRNAs and ribosomes near synapses to produce proteins locally. A relative paucity of polyribosomes (considered the active sites of translation) detected in electron micrographs of neuronal processes (axons and dendrites), however, has suggested a rather limited capacity for local protein synthesis. Polysome profiling together with ribosome footprinting of microdissected synaptic regions revealed that a surprisingly high number of dendritic and/or axonal transcripts were predominantly associated with monosomes (single ribosomes). Contrary to prevailing views, the neuronal monosomes were in the process of active protein synthesis (e.g. they exhibited elongation). Most mRNAs showed a similar translational status in both compartments, but some transcripts exhibited differential ribosome occupancy in the somata and neuropil. Strikingly, monosome-preferred transcripts often encoded high-abundance synaptic proteins. This work suggests a significant contribution of monosome translation to the maintenance of the local neuronal proteome. This mode of translation can presumably solve some of restricted space issues (given the large size of polysomes) and also increase the diversity of proteins made from a limited number of ribosomes available in dendrites and axons.

scholarly journals Cortical wiring by synapse-specific control of local protein synthesis

2021 ◽  
Author(s):  
Clémence Bernard ◽  
David Exposito-Alonso ◽  
Martijn Selten ◽  
Stella Sanalidou ◽  
Alicia Hanusz-Godoy ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Synapse Formation ◽  
Mrna Translation ◽  
Protein Translation ◽  
Synaptic Proteins ◽  
Local Synthesis ◽  
Local Protein Synthesis ◽  
Mouse Cerebral Cortex ◽  
A Cell ◽  
Local Protein

Neurons use local protein synthesis as a mechanism to support their morphological complexity, which requires independent control across multiple subcellular compartments including individual synapses. However, to what extent local translation is differentially regulated at the level of specific synaptic connections remains largely unknown. Here, we identify a signaling pathway that regulates the local synthesis of proteins required for the formation of excitatory synapses on parvalbumin-expressing (PV+) interneurons in the mouse cerebral cortex. This process involves the regulation of the mTORC1 inhibitor Tsc2 by the receptor tyrosine kinase ErbB4, which enables the local control of mRNA translation in a cell type-specific and synapse-specific manner. Ribosome-associated mRNA profiling reveals a molecular program of synaptic proteins that regulates the formation of excitatory inputs on PV+ interneurons downstream of ErbB4 signaling. Our work demonstrates that local protein translation is regulated at the level of specific connections to control synapse formation in the nervous system.

scholarly journals Local protein synthesis is a ubiquitous feature of neuronal pre- and postsynaptic compartments

Science ◽  
2019 ◽  
Vol 364 (6441) ◽  
pp. eaau3644 ◽  
Author(s):  
Anne-Sophie Hafner ◽  
Paul G. Donlin-Asp ◽  
Beulah Leitch ◽  
Etienne Herzog ◽  
Erin M. Schuman
Keyword(s):  
Protein Synthesis ◽  
Mouse Brain ◽  
Metabolic Labeling ◽  
Messenger Rnas ◽  
Presynaptic Terminals ◽  
Ample Evidence ◽  
Local Protein Synthesis ◽  
Neuronal Dendrites ◽  
Brain Synaptosomes ◽  
Local Protein

There is ample evidence for localization of messenger RNAs (mRNAs) and protein synthesis in neuronal dendrites; however, demonstrations of these processes in presynaptic terminals are limited. We used expansion microscopy to resolve pre- and postsynaptic compartments in rodent neurons. Most presynaptic terminals in the hippocampus and forebrain contained mRNA and ribosomes. We sorted fluorescently labeled mouse brain synaptosomes and then sequenced hundreds of mRNA species present within excitatory boutons. After brief metabolic labeling, >30% of all presynaptic terminals exhibited a signal, providing evidence for ongoing protein synthesis. We tested different classic plasticity paradigms and observed distinct patterns of rapid pre- and/or postsynaptic translation. Thus, presynaptic terminals are translationally competent, and local protein synthesis is differentially recruited to drive compartment-specific phenotypes that underlie different forms of plasticity.

scholarly journals Spatiotemporal Insights Into RNA–Organelle Interactions in Neurons

2021 ◽  
Vol 9 ◽  
Author(s):  
Shivani C. Kharod ◽  
Dong-Woo Hwang ◽  
Sulagna Das ◽  
Young J. Yoon
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
High Resolution Imaging ◽  
Messenger Rnas ◽  
Imaging Studies ◽  
Site Specific ◽  
Local Protein Synthesis ◽  
Specific Distribution ◽  
Resolution Imaging ◽  
Local Protein

Neurons exhibit spatial compartmentalization of gene expression where localization of messenger RNAs (mRNAs) to distal processes allows for site-specific distribution of proteins through local translation. Recently, there have been reports of coordination between mRNA transport with vesicular and organellar trafficking. In this review, we will highlight the latest literature on axonal and dendritic local protein synthesis with links to mRNA–organelle cotransport followed by emerging technologies necessary to study these phenomena. Recent high-resolution imaging studies have led to insights into the dynamics of RNA–organelle interactions, and we can now peer into these intricate interactions within subcellular compartments of neurons.

Dendritic ribosomes suggest local protein synthesis during estrous synaptogenesis

Neuroreport ◽  
2003 ◽  
Vol 14 (10) ◽  
pp. 1357-1360 ◽  
Author(s):  
J. Brian McCarthy ◽  
Teresa A. Milner
Keyword(s):  
Protein Synthesis ◽  
Local Protein Synthesis ◽  
Local Protein

Hippocampal long term memory: Effect of the cholinergic system on local protein synthesis

2013 ◽  
Vol 106 ◽  
pp. 246-257 ◽  
Author(s):  
Daniele Lana ◽  
Francesca Cerbai ◽  
Jacopo Di Russo ◽  
Francesca Boscaro ◽  
Ambra Giannetti ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Memory Effect ◽  
Cholinergic System ◽  
Long Term Memory ◽  
Term Memory ◽  
Local Protein Synthesis ◽  
Local Protein

scholarly journals Differential requirement of F-actin and microtubule cytoskeleton in cue-induced local protein synthesis in axonal growth cones

2015 ◽  
Vol 10 (1) ◽  
pp. 3 ◽  
Author(s):  
Michael Piper ◽  
Aih Lee ◽  
Francisca van Horck ◽  
Heather McNeilly ◽  
Trina Lu ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Axonal Growth ◽  
Growth Cones ◽  
Microtubule Cytoskeleton ◽  
Local Protein Synthesis ◽  
Local Protein

Translating regeneration: Local protein synthesis in the neuronal injury response

2019 ◽  
Vol 139 ◽  
pp. 26-36 ◽  
Author(s):  
Sandip Koley ◽  
Meir Rozenbaum ◽  
Mike Fainzilber ◽  
Marco Terenzio
Keyword(s):  
Protein Synthesis ◽  
Neuronal Injury ◽  
Injury Response ◽  
Local Protein Synthesis ◽  
Local Protein
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