scholarly journals MoniTORing neuronal excitability at the synapse

2013 ◽  
Vol 202 (1) ◽  
pp. 7-9 ◽  
Author(s):  
Inge Kepert ◽  
Michael A. Kiebler
Keyword(s):  
Protein Synthesis ◽  
Synaptic Plasticity ◽  
Potassium Channel ◽  
Molecular Mechanism ◽  
Neuronal Excitability ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Local Translation ◽  
Local Protein Synthesis ◽  
Local Protein

Mammalian target of rapamycin (mTOR) is a key player at the synapse regulating local translation and long-lasting synaptic plasticity. Now, a new study by Sosanya et al. (2013. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201212089) investigates the molecular mechanism of how mTOR suppresses local protein synthesis of a key potassium channel at activated synapses.

scholarly journals Object-based analyses in FIJI/ImageJ to measure local RNA translation sites in neurites in response to Aβ1-42 oligomers

2020 ◽  
Author(s):  
María Gamarra ◽  
Maite Blanco-Urrejola ◽  
Andreia F.R. Batista ◽  
Josune Imaz ◽  
Jimena Baleriola
Keyword(s):  
Protein Synthesis ◽  
Protein Delivery ◽  
Hippocampal Neurons ◽  
Rna Localization ◽  
Laplacian Operator ◽  
Local Translation ◽  
Local Protein Synthesis ◽  
Rna Translation ◽  
Object Based ◽  
Local Protein

AbstractSubcellular protein delivery is especially important in signal transduction and cell behavior, and is typically achieved by localization signals within the protein. However, protein delivery can also rely on localization of mRNAs that are translated at target sites. Although once considered heretical, RNA localization has proven to be highly conserved in eukaryotes.RNA localization and localized translation are especially relevant in polarized cells like neurons where neurites extend dozens to hundreds of centimeters away from the soma. Local translation confers dendrites and axons the capacity to respond to their environment in an acute manner without fully relying on somatic signals. The relevance of local protein synthesis in neuron development, maintenance and disease has not been fully acknowledged until recent years, partly due to the limited amount of locally produced proteins. For instance, in hippocampal neurons levels of newly-synthesized somatic proteins can be more than 20-30 times greater than translation levels of neuritic proteins. Thus local translation events can be easily overlooked under the microscope.Here we describe an object-based analysis used to visualize and quantify local RNA translation sites in neurites. Newly-synthesized proteins are tagged with puromycin and endogenous RNAs labelled with SYTO. After imaging, signals corresponding to neuritic RNAs and proteins are filtered with a Laplacian operator to enhance the edges. Resulting pixels are converted into objects and selected by automatic masking followed by signal smoothing. Objects corresponding to RNA or protein and colocalized objects (RNA and protein) are quantified along individual neurites. Colocalization between RNA and protein in neurites correspond to newly-synthesized proteins arising from localized RNAs and represent localized translation sites. To test the validity of our analyses we have compared control neurons to Aβ1-42-treated neurons. Aβ is involved in the pathology of Alzheimer’s disease and was previously reported to induce local translation in axons and dendrites which in turn contributes to the disease. We have observed that Aβ increases the synthesis of neuritic proteins as well as the fraction of translating RNAs in distal sites of the neurite, suggesting an induction of local protein synthesis. Our results thus confirm previous reports and validate our quantification method.

scholarly journals Microglia perform local protein synthesis at perisynaptic and phagocytic structures

2021 ◽  
Author(s):  
Michael J. Vasek ◽  
Jelani D. Deajon-Jackson ◽  
Yating Liu ◽  
Haley W. Crosby ◽  
Jiwon Yi ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
De Novo ◽  
Protein Translation ◽  
Local Translation ◽  
Slice Preparation ◽  
Local Protein Synthesis ◽  
Phagocytic Cups ◽  
Regulate Protein ◽  
Lysosomal Proteins ◽  
Local Protein

AbstractRecent studies have illuminated the importance of several key signaling pathways in regulating the dynamic surveillance and phagocytic activity of microglia. Yet little is known about how these signals result in the assembly of phagolysosomal machinery near targets of phagocytosis, especially in processes distal from the microglial soma. Neurons, astrocytes, and oligodendrocytes locally regulate protein translation within distal processes. Therefore, we tested whether there is regulated local translation within peripheral microglia processes (PeMPs). We show that PeMPs contain ribosomes which engage in de novo protein synthesis, and these associate with a subpool of transcripts involved in pathogen defense, motility, and phagocytosis. Using a live slice preparation, we further show that acute translation blockade impairs the formation of PeMP phagocytic cups, the localization of lysosomal proteins within them, and phagocytosis. Collectively, these data argue for a regulated local translation in PeMPs and indicate a need for new translation to support dynamic microglial function.

scholarly journals Selective role of the translin/trax RNase complex in hippocampal synaptic plasticity

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Alan Jung Park ◽  
Mahesh Shivarama Shetty ◽  
Jay M. Baraban ◽  
Ted Abel
Keyword(s):  
Protein Synthesis ◽  
Synaptic Plasticity ◽  
Molecular Mechanisms ◽  
Metabotropic Glutamate Receptor ◽  
Fragile X ◽  
Local Protein Synthesis ◽  
Hippocampal Synaptic Plasticity ◽  
Behavioral Abnormalities ◽  
Local Protein

Abstract Activity-dependent local protein synthesis is critical for synapse-specific, persistent plasticity. Abnormalities in local protein synthesis have been implicated in psychiatric disorders. We have recently identified the translin/trax microRNA-degrading enzyme as a novel mediator of protein synthesis at activated synapses. Additionally, translin knockout (KO) mice, which lack translin/trax, exhibit some of the behavioral abnormalities found in a mouse model of fragile X syndrome (fragile X mental retardation protein-FMRP-KO mice). Therefore, identifying signaling pathways interacting with translin/trax to support persistent synaptic plasticity is a translationally relevant goal. Here, as a first step to achieve this goal, we have assessed the requirement of translin/trax for multiple hippocampal synaptic plasticity paradigms that rely on distinct molecular mechanisms. We found that mice lacking translin/trax exhibited selective impairment in a form of persistent hippocampal plasticity, which requires postsynaptic protein kinase A (PKA) activity. In contrast, enduring forms of plasticity that are dependent on presynaptic PKA were unaffected. Furthermore, these mice did not display exaggerated metabotropic glutamate receptor-mediated long-term synaptic depression (mGluR-LTD), a hallmark of the FMRP KO mice. On the contrary, translin KO mice exhibited deficits in N-methyl-d-aspartate receptor (NMDAR) dependent LTD, a phenotype not observed in the FMRP knockouts. Taken together, these findings demonstrate that translin/trax mediates long-term synaptic plasticity that is dependent on postsynaptic PKA signaling and suggest that translin/trax and FMRP play distinct roles in hippocampal synaptic plasticity.

scholarly journals BDNF-induced local protein synthesis and synaptic plasticity

2014 ◽  
Vol 76 ◽  
pp. 639-656 ◽  
Author(s):  
Graciano Leal ◽  
Diogo Comprido ◽  
Carlos B. Duarte
Keyword(s):  
Protein Synthesis ◽  
Synaptic Plasticity ◽  
Local Protein Synthesis ◽  
Local Protein

scholarly journals Selective role of the translin/trax RNase complex in hippocampal synaptic plasticity

2020 ◽  
Author(s):  
Alan Jung Park ◽  
Mahesh Shivarama Shetty ◽  
Jay M. Baraban ◽  
Ted Abel
Keyword(s):  
Protein Synthesis ◽  
Synaptic Plasticity ◽  
Molecular Mechanisms ◽  
Metabotropic Glutamate Receptor ◽  
Fragile X ◽  
Local Protein Synthesis ◽  
Hippocampal Synaptic Plasticity ◽  
Behavioral Abnormalities ◽  
Local Protein

Abstract Activity-dependent local protein synthesis is critical for synapse-specific, persistent plasticity. Abnormalities in local protein synthesis have been implicated in psychiatric disorders. We have recently identified the translin/trax microRNA-degrading enzyme as a novel mediator of protein synthesis at activated synapses. Additionally, translin knockout (KO) mice, which lack translin/trax, exhibit some of the behavioral abnormalities found in a mouse model of fragile X syndrome (fragile X mental retardation protein-FMRP-KO mice). Therefore, identifying signaling pathways interacting with translin/trax to support persistent synaptic plasticity is a translationally relevant goal. Here, as a first step to achieve this goal, we have assessed the requirement of translin/trax for multiple hippocampal synaptic plasticity paradigms that rely on distinct molecular mechanisms. We found that mice lacking translin/trax exhibited selective impairment in a form of persistent hippocampal plasticity, which requires postsynaptic protein kinase A (PKA) activity. In contrast, enduring forms of plasticity that are dependent on presynaptic PKA were unaffected. Furthermore, these mice did not display exaggerated metabotropic glutamate receptor-mediated long-term synaptic depression (mGluR-LTD), a hallmark of the FMRP KO mice. . On the contrary, translin KO mice exhibited deficits in N-methyl-D-aspartate receptor (NMDAR) dependent LTD, a phenotype not observed in the FMRP knockouts. Taken together, these findings demonstrate that translin/trax mediates long-term synaptic plasticity that is dependent on postsynaptic PKA signaling and suggest that translin/trax and FMRP play distinct roles in hippocampal synaptic plasticity.

scholarly journals RNA Localization and Local Translation in Glia in Neurological and Neurodegenerative Diseases: Lessons from Neurons

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 632
Author(s):  
Maite Blanco-Urrejola ◽  
Adhara Gaminde-Blasco ◽  
María Gamarra ◽  
Aida de la Cruz ◽  
Elena Vecino ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Neurodegenerative Diseases ◽  
Protein Delivery ◽  
Local Translation ◽  
Protein Distribution ◽  
Local Protein Synthesis ◽  
Target Sites ◽  
Art Research ◽  
Cellular Compartments ◽  
Local Protein

Cell polarity is crucial for almost every cell in our body to establish distinct structural and functional domains. Polarized cells have an asymmetrical morphology and therefore their proteins need to be asymmetrically distributed to support their function. Subcellular protein distribution is typically achieved by localization peptides within the protein sequence. However, protein delivery to distinct cellular compartments can rely, not only on the transport of the protein itself but also on the transport of the mRNA that is then translated at target sites. This phenomenon is known as local protein synthesis. Local protein synthesis relies on the transport of mRNAs to subcellular domains and their translation to proteins at target sites by the also localized translation machinery. Neurons and glia specially depend upon the accurate subcellular distribution of their proteome to fulfil their polarized functions. In this sense, local protein synthesis has revealed itself as a crucial mechanism that regulates proper protein homeostasis in subcellular compartments. Thus, deregulation of mRNA transport and/or of localized translation can lead to neurological and neurodegenerative diseases. Local translation has been more extensively studied in neurons than in glia. In this review article, we will summarize the state-of-the art research on local protein synthesis in neuronal function and dysfunction, and we will discuss the possibility that local translation in glia and deregulation thereof contributes to neurological and neurodegenerative diseases.

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