scholarly journals Calmodulin binds the N-terminus of the functional amyloid Orb2A inhibiting fibril formation

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0259872
Author(s):  
Maria A. Soria ◽  
Silvia A. Cervantes ◽  
Ansgar B. Siemer
Keyword(s):  
Lipid Membranes ◽  
Ex Vivo ◽  
Fibril Formation ◽  
Long Term Memory ◽  
Amphipathic Helix ◽  
Cytoplasmic Polyadenylation ◽  
N Terminus ◽  
Element Binding Protein

The cytoplasmic polyadenylation element-binding protein Orb2 is a key regulator of long-term memory (LTM) in Drosophila. The N-terminus of the Orb2 isoform A is required for LTM and forms cross-β fibrils on its own. However, this N-terminus is not part of the core found in ex vivo fibrils. We previously showed that besides forming cross-β fibrils, the N-terminus of Orb2A binds anionic lipid membranes as an amphipathic helix. Here, we show that the Orb2A N-terminus can similarly interact with calcium activated calmodulin (CaM) and that this interaction prevents fibril formation. Because CaM is a known regulator of LTM, this interaction could potentially explain the regulatory role of Orb2A in LTM.

Role of CPEB-Family Proteins in Memory

2020 ◽  
Author(s):  
Kausik Si
Keyword(s):  
Molecular Mechanisms ◽  
Family Members ◽  
Long Term Memory ◽  
Cytoplasmic Polyadenylation ◽  
Element Binding Protein ◽  
The Face ◽  
Specific Mrnas ◽  
Over Time

A synapse-based mechanism of formation and persistence of long-term memory (LTM) entails some unique mechanistic challenges. It requires experience-dependent changes in synapse composition, function, and number. These changes must be specific to the synapse of interest, although all synapses in a neuron rely on the same genome. Finally, these changes must persist over time in the face of constant synaptic protein turnover. It has long been known that translation at the synapse is one of the fundamental requirements for LTM, and multiple mechanisms of synaptic translation have been characterized. Among these translation regulatory mechanisms, cytoplasmic polyadenylation element binding protein (CPEB) family members fulfill some of the unique needs of LTM and can even be considered as contributing to the biochemical substrates of memory. These proteins orchestrate a “synaptic mark” and regulate translation of specific mRNAs required for changes in synaptic composition, function, and number. Some CPEB family members also self-assemble and alter their function to maintain the altered synaptic state over time, contributing to persistence of memory. This chapter summarizes the known function of different CPEB family members in memory, their underlying molecular mechanisms, and important issues that remain to be resolved.

scholarly journals The CPEB3 ribozyme modulates hippocampal-dependent memory

2021 ◽  
Author(s):  
Claire C. Chen ◽  
Joseph Han ◽  
Carlene A. Chinn ◽  
Xiang Li ◽  
Mehran Nikan ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Antisense Oligonucleotide ◽  
Long Term Memory ◽  
Cytoplasmic Polyadenylation ◽  
Term Memory ◽  
Mrna Maturation ◽  
Element Binding Protein ◽  
Cultured Cortical Neurons ◽  
Underlying Mechanisms

AbstractA self-cleaving ribozyme mapping to an intron of the cytoplasmic polyadenylation element binding protein 3 (CPEB3) gene has been suggested to play a role in human episodic memory, but the underlying mechanisms mediating this effect are not known. The ribozymes maps to the second intron of the CPEB3 gene and its self-scission half-life matches the time it takes an RNA polymerase to reach the immediate downstream exon, suggesting that the ribozyme-dependent intron cleavage is tuned to co-transcriptional splicing of the CPEB3 mRNA. Here we report that the murine ribozyme modulates its own host mRNA maturation in both cultured cortical neurons and the hippocampus. Inhibition of the ribozyme using an antisense oligonucleotide leads to increased CPEB3 protein expression, which enhances polyadenylation and translation of localized plasticity-related target mRNAs, and subsequently strengthens hippocampal-dependent long-term memory. These findings reveal a previously unknown role for self-cleaving ribozyme activity in regulating experience-induced co-transcriptional and local translational processes required for learning and memory.

scholarly journals Consolidation of Memory After its Reactivation: Involvement of ß Noradrenergic Receptors in the Late Phase

1998 ◽  
Vol 6 (3) ◽  
pp. 63-68 ◽  
Author(s):  
Pascal Roullet ◽  
Susan Sara
Keyword(s):  
Late Phase ◽  
Long Term Memory ◽  
Control Groups ◽  
Camp Pathway ◽  
Noradrenergic Receptors ◽  
Element Binding Protein ◽  
Responsive Element ◽  
Camp Responsive Element Binding

Evidence is growing that the cAMP pathway through the cAMP responsive element binding protein (CREB) transcription factor plays an important role in long-term memory formation (LTM). To study the role of ß-noradrenergic receptors, positively linked to the cAMP secondmessenger system, in the dynamics of LTM processes, we used a memory-reactivation paradigm because recent studies in our laboratory confirmed that reactivated memory is labile and undergoes an extended reconsolidation process. In an eight-arm maze, rats were trained to choose the same three baited arms; 24 hr later, memory was reactivated and then the rats were injected intracerebroventricularly at 5 min, 30 min, 60 min, or 5 hr later with the ß-antagonist timolol or with saline. The results showed that injection of timolol induced amnesia only at the 60 min post-reactivation interval, whereas all control groups and groups that were timolol-injected at other post-reactivation intervals displayed optimal retention. The delayed amnesic action of timoloi suggests that ß noradrenergic receptors and the cAMP cascade are implicated in the late phase of reprocessing of a remembered event.

scholarly journals Oiling the gears of memory: quercetin exposure during memory formation, consolidation, and recall enhances memory in Lymnaea stagnalis

2021 ◽  
Author(s):  
VERONICA RIVI ◽  
Anurada Batabyal ◽  
Cristina Benatti ◽  
Joan JMC Blom ◽  
Fabio Tascedda ◽  
...  
Keyword(s):  
Lymnaea Stagnalis ◽  
Memory Formation ◽  
Long Term Memory ◽  
Short Term ◽  
Extrinsic Factors ◽  
Element Binding Protein ◽  
Integral Process ◽  
Cyclic Amp Response Element

Memory formation (short-term, intermediate-term, and long-term) is an integral process of cognition which allows individuals to retain important information and is influenced by various intrinsic and extrinsic factors. A major extrinsic factor influencing cognition across taxa is diet, which may contain rich sources of molecular agents with antioxidant, anti-inflammatory, and memory enhancing properties that potentially enhance cognitive ability. A common and abundant flavonoid present in numerous food substances is quercetin (Q) which is also known to upregulate cyclic AMP response element binding protein (CREB) in several animals including our model system Lymnaea stagnalis. Since CREB is known to be involved in long term memory (LTM) formation, we investigated the role of Q-exposure on memory formation, consolidation, and recall during operant conditioning of aerial respiratory behaviour in Lymnaea. Snails were exposed to Q 3h before or after training to ascertain its effects on LTM. Additionally, we investigated the effect of the combined presentation of a single reinforcing stimulus (at 24h post-training or 24h before training) and Q-exposure on both LTM formation and reconsolidation. Our data indicate that Q-exposure acts on the different phases of memory formation, consolidation, and recall leading to enhanced LTM formation.

scholarly journals The low complexity motif of cytoplasmic polyadenylation element binding protein 3 (CPEB3) is critical for the trafficking of its targets in neurons

2020 ◽  
Author(s):  
Lenzie Ford ◽  
Arun Asok ◽  
Arielle D. Tripp ◽  
Cameron Parro ◽  
Michelle Fitzpatrick ◽  
...  
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Low Complexity ◽  
Long Term Memory ◽  
Cytoplasmic Polyadenylation ◽  
Term Memory ◽  
Local Protein Synthesis ◽  
Element Binding Protein ◽  
Local Protein

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.

The role of PKMζ in the maintenance of long-term memory: a review

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Hamish Patel ◽  
Reza Zamani
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Long Term Potentiation ◽  
Global Memory ◽  
Long Term Memory ◽  
Compensatory Mechanism ◽  
Term Memory ◽  
Kinase C

Abstract Long-term memories are thought to be stored in neurones and synapses that undergo physical changes, such as long-term potentiation (LTP), and these changes can be maintained for long periods of time. A candidate enzyme for the maintenance of LTP is protein kinase M zeta (PKMζ), a constitutively active protein kinase C isoform that is elevated during LTP and long-term memory maintenance. This paper reviews the evidence and controversies surrounding the role of PKMζ in the maintenance of long-term memory. PKMζ maintains synaptic potentiation by preventing AMPA receptor endocytosis and promoting stabilisation of dendritic spine growth. Inhibition of PKMζ, with zeta-inhibitory peptide (ZIP), can reverse LTP and impair established long-term memories. However, a deficit of memory retrieval cannot be ruled out. Furthermore, ZIP, and in high enough doses the control peptide scrambled ZIP, was recently shown to be neurotoxic, which may explain some of the effects of ZIP on memory impairment. PKMζ knockout mice show normal learning and memory. However, this is likely due to compensation by protein-kinase C iota/lambda (PKCι/λ), which is normally responsible for induction of LTP. It is not clear how, or if, this compensatory mechanism is activated under normal conditions. Future research should utilise inducible PKMζ knockdown in adult rodents to investigate whether PKMζ maintains memory in specific parts of the brain, or if it represents a global memory maintenance molecule. These insights may inform future therapeutic targets for disorders of memory loss.

scholarly journals Enhanced Antimycobacterial Response to RecombinantMycobacterium bovis BCG Expressing Latency-Associated Peptide

2001 ◽  
Vol 69 (11) ◽  
pp. 6676-6682 ◽  
Author(s):  
Ben G. Marshall ◽  
Arun Wangoo ◽  
Peadar O'Gaora ◽  
H. Terry Cook ◽  
Rory J. Shaw ◽  
...  
Keyword(s):  
Detrimental Effect ◽  
Transforming Growth Factor ◽  
Initial Response ◽  
Transforming Growth Factor Β ◽  
Mycobacterial Infection ◽  
Acute Stage ◽  
Long Term Memory ◽  
Memory Response

ABSTRACT With a view to exploring the role of transforming growth factor β (TGF-β) during mycobacterial infection, recombinant clones of bacillus Calmette-Guérin (BCG) were engineered to express the natural antagonist of TGF-β, latency-activated peptide (LAP). Induction of TGF-β activity was reduced when macrophages were infected with BCG expressing the LAP construct (LAP-BCG). There was a significant reduction in the growth of LAP-BCG in comparison to that of control BCG following intravenous infection in a mouse model. The enhanced control of mycobacterial replication was associated with an increase in the production of gamma interferon by splenocytes challenged during the acute stage of infection but with a diminished recall response assessed after 13 weeks. Organ weight and hydroxyproline content, representing tissue pathology, were also lower in mice infected with LAP-BCG. The results are consistent with the hypothesis that TGF-β has a detrimental effect on mycobacterial immunity. While a reduction in TGF-β activity augments the initial response to BCG vaccination, early bacterial clearance may adversely affect the induction of a long-term memory response by LAP-BCG.

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