scholarly journals Protein synthesis in the dendrite

2002 ◽  
Vol 357 (1420) ◽  
pp. 521-529 ◽  
Author(s):  
Shao Jun Tang ◽  
Erin M. Schuman
Keyword(s):  
Protein Synthesis ◽  
Neural Plasticity ◽  
Messenger Rna ◽  
Mrna Translation ◽  
Synaptic Activity ◽  
Synaptic Proteins ◽  
Local Source ◽  
Synaptic Protein ◽  
Specific Proteins ◽  
Molecular Nature

In neurons, many proteins that are involved in the transduction of synaptic activity and the expression of neural plasticity are specifically localized at synapses. How these proteins are targeted is not clearly understood. One mechanism is synaptic protein synthesis. According to this idea, messenger RNA (mRNA) translation from the polyribosomes that are observed at the synaptic regions provides a local source of synaptic proteins. Although an increasing number of mRNA species has been detected in the dendrite, information about the synaptic synthesis of specific proteins in a physiological context is still limited. The physiological function of synaptic synthesis of specific proteins in synaptogenesis and neural plasticity expression remains to be shown. Experiments aimed at understanding the mechanisms and functions f synaptic protein synthesis might provide important information about the molecular nature of neural plasticity.

scholarly journals Effect of post-ischaemic recovery on albumin synthesis and relative amount of translatable albumin messenger RNA in rat liver

1982 ◽  
Vol 204 (1) ◽  
pp. 197-202 ◽  
Author(s):  
G Cairo ◽  
L Schiaffonati ◽  
M G Aletti ◽  
A Bernelli-Zazzera
Keyword(s):  
Protein Synthesis ◽  
Total Protein ◽  
Messenger Rna ◽  
Relative Proportion ◽  
Liver Homogenate ◽  
Albumin Synthesis ◽  
Specific Proteins ◽  
Membrane Bound ◽  
Albumin Mrna

In liver cells recovering from reversible ischaemia, total protein synthesis by postmitochondrial supernatant and membrane-bound and free polyribosomes is not different from that in sham-operated controls. However, the relative proportion of specific proteins is changed, since the incorporation of [3H]leucine in vivo into liver albumin, relative to incorporation into total protein, as determined by precipitation of labelled albumin with the specific antibody, decreases by 40-50% in post-ischaemic livers. Cell-free synthesis by membrane-bound polyribosomes and poly(A)-enriched RNA isolated from unfractionated liver homogenate shows that the decrease in albumin synthesis in liver of rats recovering from ischaemia is due to the relative decrease in translatable albumin mRNA.

scholarly journals eIF-Three to Tango: emerging functions of translation initiation factor eIF3 in protein synthesis and disease

2020 ◽  
Vol 12 (6) ◽  
pp. 403-409 ◽  
Author(s):  
Dieter A Wolf ◽  
Yingying Lin ◽  
Haoran Duan ◽  
Yabin Cheng
Keyword(s):  
Protein Synthesis ◽  
Messenger Rna ◽  
Protein Production ◽  
Mrna Translation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Protein Homeostasis ◽  
Subcellular Targeting ◽  
Post Translational Modifications ◽  
The Past

Abstract Studies over the past three years have substantially expanded the involvements of eukaryotic initiation factor 3 (eIF3) in messenger RNA (mRNA) translation. It now appears that this multi-subunit complex is involved in every possible form of mRNA translation, controlling every step of protein synthesis from initiation to elongation, termination, and quality control in positive as well as negative fashion. Through the study of eIF3, we are beginning to appreciate protein synthesis as a highly integrated process coordinating protein production with protein folding, subcellular targeting, and degradation. At the same time, eIF3 subunits appear to have specific functions that probably vary between different tissues and individual cells. Considering the broad functions of eIF3 in protein homeostasis, it comes as little surprise that eIF3 is increasingly implicated in major human diseases and first attempts at therapeutically targeting eIF3 have been undertaken. Much remains to be learned, however, about subunit- and tissue-specific functions of eIF3 in protein synthesis and disease and their regulation by environmental conditions and post-translational modifications.

Memory Reorganization by Synaptic Protein Degradation

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
B.-K. Kaang
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Memory Retrieval ◽  
De Novo ◽  
Critical Role ◽  
Contextual Fear Conditioning ◽  
Synaptic Proteins ◽  
Protein Synthesis Inhibitor ◽  
Synaptic Protein

An accumulating body of evidence shows that the retrieval process of long-term memory is not static and requires de novo protein synthesis. Thus long-term memories are dynamic and particularly become fragile during its retrieval. Importantly, memory retrieval is regarded as a step necessary for incorporating new information into preexisting memories. We have examined whether protein degradation is involved in the memory reorganization or not. In this presentation I will present the evidence that synaptic proteins are degraded by polyubiquitination and proteasome pathway in the hippocampus after the retrieval of contextual fear conditioning. In addition, we found that the infusion of a proteasome inhibitor into the hippocampus prevented the memory impairment induced by anisomycin, a protein synthesis inhibitor. This indicates that ubiquitin/proteasome-dependent protein degradation is involved in destabilization processes accompanying the memory retrieval. It also supports our hypothesis that preexisting memory is disrupted by synaptic protein degradation before updated memory is strengthened by protein synthesis. Our data also showed that synaptic protein degradation plays a critical role in fear memory extinction, a simple form of memory reorganization. Taken together, synaptic protein degradation is critically involved in the reorganization of the preexisting memories.

scholarly journals Regulation of mRNA translation in renal physiology and disease

2009 ◽  
Vol 297 (5) ◽  
pp. F1153-F1165 ◽  
Author(s):  
Balakuntalam S. Kasinath ◽  
Denis Feliers ◽  
Kavithalakshmi Sataranatarajan ◽  
Goutam Ghosh Choudhury ◽  
Myung Ja Lee ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Protein Synthesis ◽  
Messenger Rna ◽  
Kidney Injury ◽  
Mrna Translation ◽  
Renal Physiology ◽  
Physiological Adaptation ◽  
Three Stages ◽  
A Site

Translation, a process of generating a peptide from the codons present in messenger RNA, can be a site of independent regulation of protein synthesis; it has not been well studied in the kidney. Translation occurs in three stages (initiation, elongation, and termination), each with its own set of regulatory factors. Mechanisms controlling translation include small inhibitory RNAs such as microRNAs, binding proteins, and signaling reactions. Role of translation in renal injury in diabetes, endoplasmic reticulum stress, acute kidney injury, and, in physiological adaptation to loss of nephrons is reviewed here. Contribution of mRNA translation to physiology and disease is not well understood. Because it is involved in such diverse areas as development and cancer, it should prove a fertile field for investigation in renal science.

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 The mRNA translation landscape in the synaptic neuropil

2020 ◽  
Author(s):  
Caspar Glock ◽  
Anne Biever ◽  
Georgi Tushev ◽  
Ina Bartnik ◽  
Belquis Nassim-Assir ◽  
...  
Keyword(s):  
Translational Control ◽  
Brain Slices ◽  
Mrna Translation ◽  
Synaptic Proteins ◽  
Synaptic Protein ◽  
Synaptic Connections ◽  
Rna Seq ◽  
Rodent Brain ◽  
A Minor ◽  
Specific Mrna

AbstractTo form and modify synaptic connections and store information, neurons continuously remodel their proteomes. The impressive length of dendrites and axons imposes unique logistical challenges to maintain synaptic proteins at locations remote from the transcription source (the nucleus). The discovery of thousands of mRNAs near synapses suggested that neurons overcome distance and gain autonomy by producing proteins locally1. It is not known, however if, how and when localized mRNAs are translated into protein. To investigate the translational landscape in neuronal subregions, we performed simultaneous RNA-seq and Ribo-seq from microdissected rodent brain slices to identify and quantify the transcriptome and translatome in cell bodies as well as dendrites and axons (neuropil). More than 4800 transcripts were translated in synaptic regions. Thousands of transcripts were differentially translated between somatic and synaptic regions, with scaffold and signaling molecules mostly arising from local sources. Furthermore, specific mRNA features were identified that regulate the efficiency of mRNA translation. The findings overturn the view that local translation is a minor source of synaptic protein2 and indicate that on-site translational control is an important mechanism to control synaptic strength.

scholarly journals Activity-dependent changes in synaptic protein complex composition are consistent in different detergents despite differential solubility

2019 ◽  
Author(s):  
Jonathan D. Lautz ◽  
Edward P. Gniffke ◽  
Emily A. Brown ◽  
Karen B. Immendorf ◽  
Ryan D. Mendel ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Protein Complexes ◽  
Synaptic Activity ◽  
Synaptic Proteins ◽  
Size Exclusion ◽  
Synaptic Protein ◽  
Exclusion Chromatography ◽  
Associated Proteins ◽  
Dependent Protein ◽  
Activity Dependent

AbstractAt the post-synaptic density (PSD), large protein complexes dynamically form and dissociate in response to synaptic activity, comprising the biophysical basis for learning and memory. The use of detergents to both isolate the PSD fraction and release its membrane-associated proteins complicates studies of these activity-dependent protein interaction networks, because detergents can simultaneously disrupt the very interactions under study. Despite widespread recognition that different detergents yield different experimental results, the effect of detergent on activity-dependent synaptic protein complexes has not been rigorously examined. Here, we characterize the effect of three detergents commonly used to study synaptic proteins on activity-dependent protein interactions. We first demonstrate that SynGAP-containing interactions are more abundant in 1% Deoxycholate (DOC), while Shank-, Homer-and mGluR5-containing interactions are more abundant in 1% NP-40 or Triton. All interactions were detected preferentially in high molecular weight (HMW) complexes generated by size exclusion chromatography, although the detergent-specific abundance of proteins in HMW fractions did not correlate with the abundance of detected interactions. Activity-dependent changes in protein complexes were consistent across detergent types, suggesting that detergents do not isolate distinct protein pools with unique behaviors. However, detection of activity-dependent changes is more or less feasible in different detergents due to baseline solubility. Collectively, our results demonstrate that detergents affect the solubility of individual proteins, but activity-dependent changes in protein interactions, when detectable, are consistent across detergent types.

Genes

2019 ◽  
pp. 162-185
Keyword(s):  
Environmental Factors ◽  
Messenger Rna ◽  
Point Mutations ◽  
Mrna Translation ◽  
Dna Bases ◽  
Small Scale ◽  
Genetic Mutations ◽  
Base Pairs ◽  
Frameshift Mutations ◽  
Specific Proteins

Genes are regions on DNA that contain the instructions for making specific proteins. In humans, genes vary in size from hundreds of DNA bases to over 3 million base pairs. From DNA to proteins, two steps are involved. Transcription is accessing the gene and reading the instructions therein in the nucleus producing as a single strand of RNA called messenger RNA (mRNA). Translation is reading the instructions on mRNA to assemble the specified proteins on the surface of ribosomes. Genetic mutations are heritable, small-scale alterations in one or more base pairs that damage DNA. Although new mutations introduce new variation, these are constantly removed from populations. Mutations can arise naturally during DNA replication or can be caused by environmental factors like chemicals or radiation. They can be harmful, neutral, or beneficial to the organism and are generally of five types: point mutations, frameshift mutations, transposons, transitions, and transversions. This chapter explores this aspect of genes.

scholarly journals MAP2 is differentially phosphorylated in schizophrenia, altering its function

2021 ◽  
Author(s):  
M. J. Grubisha ◽  
X. Sun ◽  
M. L. MacDonald ◽  
M. Garver ◽  
Z. Sun ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Disease Risk ◽  
Protein Translation ◽  
Synaptic Proteins ◽  
Synaptic Protein ◽  
Spine Density ◽  
Neuronal Structure ◽  
Protein Levels ◽  
And Function

AbstractSchizophrenia (Sz) is a highly polygenic disorder, with common, rare, and structural variants each contributing only a small fraction of overall disease risk. Thus, there is a need to identify downstream points of convergence that can be targeted with therapeutics. Reduction of microtubule-associated protein 2 (MAP2) immunoreactivity (MAP2-IR) is present in individuals with Sz, despite no change in MAP2 protein levels. MAP2 is phosphorylated downstream of multiple receptors and kinases identified as Sz risk genes, altering its immunoreactivity and function. Using an unbiased phosphoproteomics approach, we quantified 18 MAP2 phosphopeptides, 9 of which were significantly altered in Sz subjects. Network analysis grouped MAP2 phosphopeptides into three modules, each with a distinct relationship to dendritic spine loss, synaptic protein levels, and clinical function in Sz subjects. We then investigated the most hyperphosphorylated site in Sz, phosphoserine1782 (pS1782). Computational modeling predicted phosphorylation of S1782 reduces binding of MAP2 to microtubules, which was confirmed experimentally. We generated a transgenic mouse containing a phosphomimetic mutation at S1782 (S1782E) and found reductions in basilar dendritic length and complexity along with reduced spine density. Because only a limited number of MAP2 interacting proteins have been previously identified, we combined co-immunoprecipitation with mass spectrometry to characterize the MAP2 interactome in mouse brain. The MAP2 interactome was enriched for proteins involved in protein translation. These associations were shown to be functional as overexpression of wild type and phosphomimetic MAP2 reduced protein synthesis in vitro. Finally, we found that Sz subjects with low MAP2-IR had reductions in the levels of synaptic proteins relative to nonpsychiatric control (NPC) subjects and to Sz subjects with normal and MAP2-IR, and this same pattern was recapitulated in S1782E mice. These findings suggest a new conceptual framework for Sz—that a large proportion of individuals have a “MAP2opathy”—in which MAP function is altered by phosphorylation, leading to impairments of neuronal structure, synaptic protein synthesis, and function.

scholarly journals MAP2 is Differentially Phosphorylated in Schizophrenia, Altering its Function

2019 ◽  
Author(s):  
MJ Grubisha ◽  
X Sun ◽  
ML MacDonald ◽  
M Garver ◽  
Z Sun ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Disease Risk ◽  
Protein Translation ◽  
Synaptic Proteins ◽  
Synaptic Protein ◽  
Spine Density ◽  
Neuronal Structure ◽  
Protein Levels ◽  
And Function

AbstractSchizophrenia (Sz) is a highly polygenic disorder, with common, rare, and structural variants each contributing only a small fraction of overall disease risk. Thus, there is a need to identify downstream points of convergence that can be targeted with therapeutics. Reduction of Microtubule-associated Protein 2 (MAP2) immunoreactivity (MAP2-IR) is present in individuals with Sz, despite no change in MAP2 protein levels. MAP2 is phosphorylated downstream of multiple receptors and kinases identified as Sz risk genes, altering its immunoreactivity and function. Using an unbiased phosphoproteomics approach we quantified 18 MAP2 phosphopeptides, 9 of which were significantly altered in Sz subjects. Network analysis grouped MAP2 phosphopeptides into 3 modules, each with a distinct relationship to dendritic spine loss, synaptic protein levels, and clinical function in Sz subjects. We then investigated the most hyperphosphorylated site in Sz, phosphoserine1782 (pS1782). Computational modeling predicted phosphorylation of S1782 reduces binding of MAP2 to microtubules, which was confirmed experimentally. We generated a transgenic mouse containing a phosphomimetic mutation at S1782 (S1782E) and found reductions in basilar dendritic length and complexity along with reduced spine density. Because only a limited number of MAP2 interacting proteins have been previously identified, we combined co-immunoprecipitation with mass spectrometry to characterize the MAP2 interactome in mouse brain. The MAP2 interactome was enriched for proteins involved in protein translation. These associations were shown to be functional as overexpression of wildtype and phosphomimetic MAP2 reduced protein synthesis in vitro. Finally, we found that Sz subjects with low MAP2-IR had reductions in the levels of synaptic proteins relative to nonpsychiatric control (NPC) subjects and to Sz subjects with normal and MAP2-IR, and this same pattern was recapitulated in S1782E mice. These findings suggest a new conceptual framework for Sz - that a large proportion of individuals have a “MAP2opathy” - in which MAP function is altered by phosphorylation, leading to impairments of neuronal structure, synaptic protein synthesis, and function.

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