scholarly journals A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs

2020 ◽  
Vol 6 (11) ◽  
pp. eaaz1588 ◽  
Author(s):  
Sebastian Baumann ◽  
Artem Komissarov ◽  
Maria Gili ◽  
Verena Ruprecht ◽  
Stefan Wieser ◽  
...  
Keyword(s):  
Transport System ◽  
Mammalian Cells ◽  
Cell Polarization ◽  
Long Term Memory ◽  
Asymmetric Distribution ◽  
Messenger Rnas ◽  
Mrna Transport ◽  
Transport Efficiency ◽  
Essential Components

Through the asymmetric distribution of messenger RNAs (mRNAs), cells spatially regulate gene expression to create cytoplasmic domains with specialized functions. In neurons, mRNA localization is required for essential processes such as cell polarization, migration, and synaptic plasticity underlying long-term memory formation. The essential components driving cytoplasmic mRNA transport in neurons and mammalian cells are not known. We report the first reconstitution of a mammalian mRNA transport system revealing that the tumor suppressor adenomatous polyposis coli (APC) forms stable complexes with the axonally localized β-actin and β2B-tubulin mRNAs, which are linked to a kinesin-2 via the cargo adaptor KAP3. APC activates kinesin-2, and both proteins are sufficient to drive specific transport of defined mRNA packages. Guanine-rich sequences located in 3′UTRs of axonal mRNAs increase transport efficiency and balance the access of different mRNAs to the transport system. Our findings reveal a minimal set of proteins sufficient to transport mammalian mRNAs.

scholarly journals A reconstituted mammalian APC-kinesin complex selectively transports defined packages of mRNAs

2019 ◽  
Author(s):  
Sebastian Baumann ◽  
Artem Komissarov ◽  
Maria Gili ◽  
Verena Ruprecht ◽  
Stefan Wieser ◽  
...  
Keyword(s):  
Transport System ◽  
Mammalian Cells ◽  
Cell Polarization ◽  
Long Term Memory ◽  
Asymmetric Distribution ◽  
Mrna Transport ◽  
Transport Efficiency ◽  
Essential Components ◽  
First Time

AbstractThrough the asymmetric distribution of mRNAs cells spatially regulate gene expression to create cyto-plasmic domains with specialized functions. In mammalian neurons, mRNA localization is required for essential processes as cell polarization, migration and synaptic plasticity underlying long-term memory formation. The essential components driving cytoplasmic mRNA transport in neurons and mammalian cells are not known. Here, we report the first reconstitution of a mammalian mRNA transport system revealing that the tumour suppressor adenomatous polyposis coli (APC) forms stable complexes with the axonally localised β-actin and β2B-tubulin mRNAs which are linked to a heterotrimeric kinesin-2 via the cargo adaptor KAP3. APC activates kinesin-2 and both proteins are sufficient to drive specific transport of defined mRNA packages. Guanine-rich sequences located in 3’UTRs of axonal mRNAs increase transport efficiency and balance the access of different mRNAs to the transport system. Our findings reveal for the first time a minimal set of proteins capable of driving kinesin-based, mammalian mRNA transport.

scholarly journals Protein phase separation provides long-term memory of transient spatial stimuli

2018 ◽  
Author(s):  
Elliot Dine ◽  
Agnieszka A. Gil ◽  
Giselle Uribe ◽  
Clifford P. Brangwynne ◽  
Jared E. Toettcher
Keyword(s):  
Phase Separation ◽  
Spatial Memory ◽  
Tyrosine Kinases ◽  
Long Term Memory ◽  
Asymmetric Distribution ◽  
List Type ◽  
Term Memory ◽  
Biophysical Process ◽  
Cytoskeletal Responses

AbstractProtein/RNA clusters arise frequently in spatially-regulated biological processes, from the asymmetric distribution of P granules and PAR proteins in developing embryos to localized receptor oligomers in migratory cells. This co-occurrence suggests that protein clusters might possess intrinsic properties that make them a useful substrate for spatial regulation. Here, we demonstrate that protein droplets show a robust form of spatial memory, maintaining the spatial pattern of an inhibitor of droplet formation long after it has been removed. Despite this persistence, droplets can be highly dynamic, continuously exchanging monomers with the diffuse phase. We investigate the principles of biophysical spatial memory in three contexts: a computational model of phase separation; a novel optogenetic system where light can drive rapid, localized dissociation of liquid-like protein droplets; and membrane-localized signal transduction from clusters of receptor tyrosine kinases. Our results suggest that the persistent polarization underlying many cellular and developmental processes could arise through a simple biophysical process, without any additional requirement for biochemical positive and negative feedback loops.HighlightsWe introduce PixELLs, an optogenetic system for protein droplet disassembly.Modeling and experiments demonstrate long-term memory of local droplet dissociation.Droplets ‘remember’ spatial stimuli in nuclei, the cytosol and on cell membranes.FGFR-optoDroplets convert transient local inputs to persistent cytoskeletal responses.

scholarly journals Expression Signature of lncRNAs and mRNAs in Sevoflurane-Induced Mouse Brain Injury: Implication of Involvement of Wide Molecular Networks and Pathways

2021 ◽  
Vol 22 (3) ◽  
pp. 1389
Author(s):  
Congshan Jiang ◽  
Thiago Arzua ◽  
Yasheng Yan ◽  
Xiaowen Bai
Keyword(s):  
Mrna Expression ◽  
Expression Profiles ◽  
Risk Groups ◽  
Bioinformatic Analysis ◽  
Brain Cell ◽  
Learning Ability ◽  
Molecular Networks ◽  
Long Term Memory ◽  
Messenger Rnas

Sevoflurane, one of the most commonly used pediatric anesthetics, was found to cause developmental neurotoxicity. To understand specific risk groups and develop countermeasures, a better understanding of its mechanisms is needed. We hypothesize that, as in many other brain degeneration pathways, long non-coding RNAs (lncRNAs) are involved in the sevoflurane-induced neurotoxicity. Postnatal day 7 (PD7) mice were exposed to 3% sevoflurane for 6 h. To quantify neurotoxicity in these mice, we (1) detected neural apoptosis through analysis of caspase 3 expression level and activity and (2) assessed long-term learning ability via the Morris water maze at PD60. To elucidate specific mechanisms, profiles of 27,427 lncRNAs and 18,855 messenger RNAs (mRNAs) in mouse hippocampi were analyzed using microarray assays. Sevoflurane-induced abnormal lncRNA and mRNA expression-associated function pathways were predicted by bioinformatic analysis. We found that sevoflurane induced significant neurotoxicity, causing acute neuroapoptosis and abnormal expression of 148 mRNAs and 301 lncRNAs on PD7 in mouse hippocampus. Additionally, exposed mice exhibited impaired memory on PD60. Bioinformatic analysis predicted that the dysregulated mRNAs, which are highly correlated with their co-expressed dysregulated lncRNAs, might be involved in 34 neurodegenerative signaling pathways (e.g., brain cell apoptosis and intellectual developmental disorder). Our study reveals for the first time that neonatal exposure to 3% sevoflurane induces abnormal lncRNA and mRNA expression profiles. These dysregulated lncRNAs/mRNAs form wide molecular networks that might contribute to various functional neurological disease pathways in the hippocampus, resulting in the observed acute apoptosis and impaired long-term memory.

Conceptual short-term memory (CSTM) supports core claims of Christiansen and Chater

2016 ◽  
Vol 39 ◽  
Author(s):  
Mary C. Potter
Keyword(s):  
Working Memory ◽  
Rapid Serial Visual Presentation ◽  
Language Comprehension ◽  
Short Term Memory ◽  
Visual Presentation ◽  
Long Term Memory ◽  
Short Term ◽  
Term Memory ◽  
Use Of Knowledge

AbstractRapid serial visual presentation (RSVP) of words or pictured scenes provides evidence for a large-capacity conceptual short-term memory (CSTM) that momentarily provides rich associated material from long-term memory, permitting rapid chunking (Potter 1993; 2009; 2012). In perception of scenes as well as language comprehension, we make use of knowledge that briefly exceeds the supposed limits of working memory.

Comparison of Auditory, Language, Memory, and Attention Abilities in Children With and Without Listening Difficulties

2020 ◽  
Vol 29 (4) ◽  
pp. 710-727
Author(s):  
Beula M. Magimairaj ◽  
Naveen K. Nagaraj ◽  
Alexander V. Sergeev ◽  
Natalie J. Benafield
Keyword(s):  
Auditory Processing ◽  
Short Term Memory ◽  
Group Differences ◽  
Long Term Memory ◽  
Short Term ◽  
Significant Group ◽  
Term Memory ◽  
Memory And Attention ◽  
Speed And Accuracy

Objectives School-age children with and without parent-reported listening difficulties (LiD) were compared on auditory processing, language, memory, and attention abilities. The objective was to extend what is known so far in the literature about children with LiD by using multiple measures and selective novel measures across the above areas. Design Twenty-six children who were reported by their parents as having LiD and 26 age-matched typically developing children completed clinical tests of auditory processing and multiple measures of language, attention, and memory. All children had normal-range pure-tone hearing thresholds bilaterally. Group differences were examined. Results In addition to significantly poorer speech-perception-in-noise scores, children with LiD had reduced speed and accuracy of word retrieval from long-term memory, poorer short-term memory, sentence recall, and inferencing ability. Statistically significant group differences were of moderate effect size; however, standard test scores of children with LiD were not clinically poor. No statistically significant group differences were observed in attention, working memory capacity, vocabulary, and nonverbal IQ. Conclusions Mild signal-to-noise ratio loss, as reflected by the group mean of children with LiD, supported the children's functional listening problems. In addition, children's relative weakness in select areas of language performance, short-term memory, and long-term memory lexical retrieval speed and accuracy added to previous research on evidence-based areas that need to be evaluated in children with LiD who almost always have heterogenous profiles. Importantly, the functional difficulties faced by children with LiD in relation to their test results indicated, to some extent, that commonly used assessments may not be adequately capturing the children's listening challenges. Supplemental Material https://doi.org/10.23641/asha.12808607

Retrieval from Memory or Procedural Strategies for Addition Problems

2011 ◽  
Vol 70 (1) ◽  
pp. 35-39 ◽  
Author(s):  
Muriel Fanget ◽  
Catherine Thevenot ◽  
Caroline Castel ◽  
Michel Fayol
Keyword(s):  
Reaction Times ◽  
Long Term Memory ◽  
Verbal Reports ◽  
Term Memory ◽  
Simple Addition ◽  
Memory Traces ◽  
Addition Problem ◽  
Retrieval From Memory ◽  
Calculation Procedures

In this study, we used a paradigm recently developed ( Thevenot, Fanget, & Fayol, 2007 ) to determine whether 10-year-old children solve simple addition problems by retrieval of the answer from long-term memory or by calculation procedures. Our paradigm is unique in that it does not rely on reaction times or verbal reports, which are known to potentially bias the results, especially in children. Rather, it takes advantage of the fact that calculation procedures degrade the memory traces of the operands, so that it is more difficult to recognize them when they have been involved in the solution of an addition problem by calculation rather than by retrieval. The present study sharpens the current conclusions in the literature and shows that, when the sum of addition problems is up to 10, children mainly use retrieval, but when it is greater than 10, they mainly use calculation procedures.

The Acute Effect of Alcohol on Various Memory Processes

2010 ◽  
Vol 24 (4) ◽  
pp. 249-252 ◽  
Author(s):  
Márk Molnár ◽  
Roland Boha ◽  
Balázs Czigler ◽  
Zsófia Anna Gaál
Keyword(s):  
Low Dose ◽  
Short Term Memory ◽  
Acute Effect ◽  
Long Term Memory ◽  
Term Memory ◽  
Memory Processes ◽  
Different Types ◽  
The Brain ◽  
Legal Consequences

This review surveys relevant and recent data of the pertinent literature regarding the acute effect of alcohol on various kinds of memory processes with special emphasis on working memory. The characteristics of different types of long-term memory (LTM) and short-term memory (STM) processes are summarized with an attempt to relate these to various structures in the brain. LTM is typically impaired by chronic alcohol intake but according to some data a single dose of ethanol may have long lasting effects if administered at a critically important age. The most commonly seen deleterious acute effect of alcohol to STM appears following large doses of ethanol in conditions of “binge drinking” causing the “blackout” phenomenon. However, with the application of various techniques and well-structured behavioral paradigms it is possible to detect, albeit occasionally, subtle changes of cognitive processes even as a result of a low dose of alcohol. These data may be important for the consideration of legal consequences of low-dose ethanol intake in conditions such as driving, etc.

Visual Search Facilitation in Repeated Displays Depends on Visuospatial Working Memory

2012 ◽  
Vol 59 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Angela A. Manginelli ◽  
Franziska Geringswald ◽  
Stefan Pollmann
Keyword(s):  
Working Memory ◽  
Visual Search ◽  
Control Experiment ◽  
Memory Load ◽  
Contextual Cueing ◽  
Long Term Memory ◽  
Visuospatial Working Memory ◽  
Working Memory Load ◽  
Memory Resources

When distractor configurations are repeated over time, visual search becomes more efficient, even if participants are unaware of the repetition. This contextual cueing is a form of incidental, implicit learning. One might therefore expect that contextual cueing does not (or only minimally) rely on working memory resources. This, however, is debated in the literature. We investigated contextual cueing under either a visuospatial or a nonspatial (color) visual working memory load. We found that contextual cueing was disrupted by the concurrent visuospatial, but not by the color working memory load. A control experiment ruled out that unspecific attentional factors of the dual-task situation disrupted contextual cueing. Visuospatial working memory may be needed to match current display items with long-term memory traces of previously learned displays.

Short- and long-term memory tasks predict working memory performance, and vice versa.

2019 ◽  
Vol 73 (2) ◽  
pp. 79-93 ◽  
Author(s):  
Ian Neath ◽  
Jean Saint-Aubin ◽  
Tamra J. Bireta ◽  
Andrew J. Gabel ◽  
Chelsea G. Hudson ◽  
...  
Keyword(s):  
Working Memory ◽  
Memory Performance ◽  
Long Term Memory ◽  
Term Memory ◽  
Short And Long Term
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