scholarly journals A continuous model of physiological prion aggregation suggests a role for Orb2 in gating long-term synaptic information

2018 ◽  
Vol 5 (12) ◽  
pp. 180336
Author(s):  
Michele Sanguanini ◽  
Antonino Cattaneo

The regulation of mRNA translation at the level of the synapse is believed to be fundamental in memory and learning at the cellular level. The family of cytoplasmic polyadenylation element binding (CPEB) proteins emerged as an important RNA-binding protein family during development and in adult neurons. Drosophila Orb2 (homologue of mouse CPEB3 protein and of the neural isoform of Aplysia CPEB) has been found to be involved in the translation of plasticity-dependent mRNAs and has been associated with long-term memory. Orb2 protein presents two main isoforms, Orb2A and Orb2B, which form an activity-induced amyloid-like functional aggregate, thought to be the translation-inducing state of the RNA-binding protein. Here we present a first two-states continuous differential model for Orb2A–Orb2B aggregation. This model provides new working hypotheses for studying the role of prion-like CPEB proteins in long-term synaptic plasticity. Moreover, this model can be used as a first step to integrate translation- and protein aggregation-dependent phenomena in synaptic facilitation rules.

2015 ◽  
Author(s):  
Michele Sanguanini ◽  
Antonino Cattaneo

The regulation of mRNA translation at synaptic level is believed to be fundamental in memory and learning at cellular level. A family of RNA binding proteins (RBPs) which emerged to be important during development and in adult neurons is the one of Cytoplasmic Polyadenylation Element Binding proteins (CPEBs). Drosophila Orb2 (homolog of vertebrate CPEB2 protein and of the neural isoform of Aplysia CPEB) has been found to be involved in the translation of plasticity-dependent mRNAs and has been associated to Long Term Memory (LTM). Orb2 protein presents two main isoforms, Orb2A and Orb2B, which form an activity induced amyloid-like functional aggregate, which is thought to be the translation-inducing state of the RBP. Here we present a two-states continuous differential model for Orb2A-Orb2B aggregation and we propose it, more generally, as a new synaptic facilitation rule for learning processes involving protein aggregation-dependent plasticity (PADP).


Author(s):  
Lenzie Ford ◽  
Arun Asok ◽  
Arielle D. Tripp ◽  
Cameron Parro ◽  
Michelle Fitzpatrick ◽  
...  

SummaryBiomolecular condensates, membraneless organelles found throughout the cell, play critical roles in many aspects of cellular function. Ribonucleoprotein granules (RNPs), a type of biomolecular condensate found in neurons that are necessary for local protein synthesis and are involved in long-term potentiation (LTP). Several RNA-binding proteins present in RNPs are necessary for the synaptic plasticity involved in LTP and long-term memory. Most of these proteins possess low complexity motifs, allowing for increased promiscuity. We explore the role the low complexity motif plays for RNA binding protein cytoplasmic polyadenylation element binding protein 3 (CPEB3), a protein necessary for long-term memory persistence. We found that RNA binding and SUMOylation are necessary for CPEB3 localization to the P body, thereby having functional implications on translation. Here, we investigate the role of the low complexity motif of CPEB3 and find that it is necessary for P body localization and downstream targeting for local protein synthesis.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Cai-Rong Yang ◽  
Gabriel Rajkovic ◽  
Enrico Maria Daldello ◽  
Xuan G. Luong ◽  
Jing Chen ◽  
...  

2020 ◽  
Vol 295 (42) ◽  
pp. 14291-14304
Author(s):  
Kathrin Bajak ◽  
Kevin Leiss ◽  
Christine Clayton ◽  
Esteban Erben

In Trypanosoma brucei and related kinetoplastids, gene expression regulation occurs mostly posttranscriptionally. Consequently, RNA-binding proteins play a critical role in the regulation of mRNA and protein abundance. Yet, the roles of many RNA-binding proteins are not understood. Our previous research identified the RNA-binding protein ZC3H5 as possibly involved in gene repression, but its role in controlling gene expression was unknown. We here show that ZC3H5 is an essential cytoplasmic RNA-binding protein. RNAi targeting ZC3H5 causes accumulation of precytokinetic cells followed by rapid cell death. Affinity purification and pairwise yeast two-hybrid analysis suggest that ZC3H5 forms a complex with three other proteins, encoded by genes Tb927.11.4900, Tb927.8.1500, and Tb927.7.3040. RNA immunoprecipitation revealed that ZC3H5 is preferentially associated with poorly translated, low-stability mRNAs, the 5′-untranslated regions and coding regions of which are enriched in the motif (U/A)UAG(U/A). As previously found in high-throughput analyses, artificial tethering of ZC3H5 to a reporter mRNA or other complex components repressed reporter expression. However, depletion of ZC3H5 in vivo caused only very minor decreases in a few targets, marked increases in the abundances of very stable mRNAs, an increase in monosomes at the expense of large polysomes, and appearance of “halfmer” disomes containing two 80S subunits and one 40S subunit. We speculate that the ZC3H5 complex might be implicated in quality control during the translation of suboptimal open reading frames.


Science ◽  
2016 ◽  
Vol 353 (6307) ◽  
pp. 1549-1552 ◽  
Author(s):  
A. Kanakkanthara ◽  
K. B. Jeganathan ◽  
J. F. Limzerwala ◽  
D. J. Baker ◽  
M. Hamada ◽  
...  

2019 ◽  
Vol 31 (3) ◽  
pp. 632
Author(s):  
Jeongwoo Kwon ◽  
Shuha Park ◽  
Min-Jung Seong ◽  
Inchul Choi ◽  
Nam-Hyung Kim

Cytoplasmic polyadenylation element binding protein (CPEB) is an RNA-binding protein that promotes elongation of poly(A) tails and regulates mRNA translation. CPEB depletion in mammary epithelium is known to disrupt tight-junction (TJ) assembly via mislocalisation of tight junction protein 1 (TJP1), but the role of CPEB in the biological functions associated with TJs has not yet been studied. The objective of this study was to investigate the roles of CPEB2 during porcine parthenote development. CPEB2 was detected in both the nuclei and apical cytoplasm at the 4- and 8-cell stages and was localised to cell–cell contact after the initiation of the morula stage. Its depletion led to retarded blastocyst formation caused by impaired TJ assembly. Moreover, transcription of TJ-associated genes, including TJP1, Coxsackie virus and adenovirus receptor (CXADR) and occludin (OCLN), was not affected, but the corresponding proteins were not properly localised at the apical cell membrane in morulae, suggesting that CPEB2 confers mRNA stability or determines subcellular localisation for translation. Remarkably reduced relative levels of TJP1 transcripts bearing the 3′-untranslated region were noted, indicating that CPEB2 mediates TJP1 mRNA stability. In conclusion, our findings demonstrate that because of its regulation of TJP1, CPEB2 is required for TJ assembly during porcine blastocyst development.


2012 ◽  
Vol 194 (24) ◽  
pp. 6900-6908 ◽  
Author(s):  
C. Michaux ◽  
C. Martini ◽  
K. Shioya ◽  
S. Ahmed Lecheheb ◽  
A. Budin-Verneuil ◽  
...  

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Mehrpouya B. Mobin ◽  
Stefanie Gerstberger ◽  
Daniel Teupser ◽  
Benedetta Campana ◽  
Klaus Charisse ◽  
...  

2019 ◽  
Vol 31 (2) ◽  
pp. 412 ◽  
Author(s):  
Jeongwoo Kwon ◽  
Shuha Park ◽  
Min-Jung Seong ◽  
Inchul Choi ◽  
Nam-Hyung Kim

Cytoplasmic polyadenylation element binding protein (CPEB) is an RNA-binding protein that promotes elongation of poly(A) tails and regulates mRNA translation. CPEB depletion in mammary epithelium is known to disrupt tight-junction (TJ) assembly via mislocalisation of tight junction protein 1 (TJP1), but the role of CPEB in the biological functions associated with TJs has not yet been studied. The objective of this study was to investigate the roles of CPEB2 during porcine parthenote development. CPEB2 was detected in both the nuclei and apical cytoplasm at the 4- and 8-cell stages and was localised to cell–cell contact after the initiation of the morula stage. Its depletion led to retarded blastocyst formation caused by impaired TJ assembly. Moreover, transcription of TJ-associated genes, including TJP1, Coxsackie virus and adenovirus receptor (CXADR) and occludin (OCLN), was not affected, but the corresponding proteins were not properly localised at the apical cell membrane in morulae, suggesting that CPEB2 confers mRNA stability or determines subcellular localisation for translation. Remarkably reduced relative levels of TJP1 transcripts bearing the 3′-untranslated region were noted, indicating that CPEB2 mediates TJP1 mRNA stability. In conclusion, our findings demonstrate that because of its regulation of TJP1, CPEB2 is required for TJ assembly during porcine blastocyst development.


2014 ◽  
Vol 15 (1) ◽  
pp. R4 ◽  
Author(s):  
Linan Chen ◽  
Jason G Dumelie ◽  
Xiao Li ◽  
Matthew HK Cheng ◽  
Zhiyong Yang ◽  
...  

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