scholarly journals Presynaptic FMRP and Local Protein Synthesis Support Structural and Functional Plasticity of Glutamatergic Axon Terminals

2021 ◽  
Author(s):  
Hannah R. Monday ◽  
Shivani Kharod ◽  
Young J. Yoon ◽  
Robert H. Singer ◽  
Pablo E. Castillo
2018 ◽  
Author(s):  
Anne-Sophie Hafner ◽  
Paul G. Donlin-Asp ◽  
Beulah Leitch ◽  
Etienne Herzog ◽  
Erin M. Schuman

AbstractThere is ample evidence for localized 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 brain slices. Most presynaptic terminals in the hippocampus and forebrain contained mRNA and ribosomes. We sorted fluorescently labeled synaptosomes from mouse brain and then sequenced hundreds of mRNA species present within excitatory boutons. After brief metabolic labeling, more them 30% of all presynaptic terminals exhibited a signal, providing evidence for ongoing protein synthesis. We tested different classic plasticity paradigms and observed unique 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.One sentence summaryProtein synthesis occurs in all synaptic compartments, including excitatory and inhibitory axon terminals.


2021 ◽  
Author(s):  
Hannah R Monday ◽  
Shivani C Kharod ◽  
Young J Yoon ◽  
Robert H Singer ◽  
Pablo E Castillo

Learning and memory critically rely on long-lasting, synapse-specific modifications. While postsynaptic forms of plasticity typically require local protein synthesis, whether and how local protein synthesis contributes to presynaptic changes remains unclear. Here, we examined the hippocampal mossy fiber (MF)-CA3 synapse which expresses both structural and functional presynaptic plasticity. We report that MF boutons synthesize protein locally and contain ribosomes. Long-term potentiation of MF-CA3 synaptic transmission (MF-LTP) was associated with translation-dependent enlargement of MF boutons. Moreover, increasing in vitro and in vivo MF activity enhanced protein synthesis in MFs. Remarkably, deletion of presynaptic Fragile X mental retardation protein (FMRP), an RNA-binding protein expressed in MF boutons and previously implicated in local postsynaptic protein synthesis-dependent plasticity, blocked structural and functional MF-LTP, suggesting that FMRP is a critical regulator of presynaptic function. Thus, presynaptic FMRP and protein synthesis dynamically control presynaptic structure and function in the mature brain.


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

2013 ◽  
Vol 106 ◽  
pp. 246-257 ◽  
Author(s):  
Daniele Lana ◽  
Francesca Cerbai ◽  
Jacopo Di Russo ◽  
Francesca Boscaro ◽  
Ambra Giannetti ◽  
...  

2015 ◽  
Vol 10 (1) ◽  
pp. 3 ◽  
Author(s):  
Michael Piper ◽  
Aih Lee ◽  
Francisca van Horck ◽  
Heather McNeilly ◽  
Trina Lu ◽  
...  

2019 ◽  
Vol 139 ◽  
pp. 26-36 ◽  
Author(s):  
Sandip Koley ◽  
Meir Rozenbaum ◽  
Mike Fainzilber ◽  
Marco Terenzio

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