Tau mRNA is present in axonal RNA granules and is associated with elongation factor 1A

Malmqvist, Tony; Anthony, Karen; Gallo, Jean‐Marc

doi:10.1016/j.brainres.2013.12.033

Cited by 14 publications

(12 citation statements)

References 17 publications

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“…We hypothesize that in polarizing neurons, tau mRNA could be locally stabilized, producing tau protein at one side of the cell ( Aronov et al, 2001 ; Dickson et al, 2013 ; Malmqvist et al, 2014 ). Polarity-mediated phosphorylation could be an alternative mechanism to regulate the local formation of tau drops in the future axon ( Herzmann et al, 2017 ; Zempel and Mandelkow, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

“…Tau drops will recruit tubulin and polymerize microtubule bundles alone or on top of pre-existing microtubules, enabling the formation of axonal microtubule bundles. A feedback loop mechanism mediated by tubulin or an enhancement of tau drops by RNA ( Malmqvist et al, 2014 ; Zhang et al, 2017 ) would be also plausible. More work on the formation of microtubule bundles in axons will be required to distinguish among these possibilities.…”

Section: Discussionmentioning

confidence: 99%

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Local Nucleation of Microtubule Bundles through Tubulin Concentration into a Condensed Tau Phase

et al. 2017

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SUMMARYNon-centrosomal microtubule bundles play important roles in cellular organization and function. Although many diverse proteins are known that can bundle microtubules, biochemical mechanisms by which cells could locally control the nucleation and formation of microtubule bundles are understudied. Here, we demonstrate that the concentration of tubulin into a condensed, liquid-like compartment composed of the unstructured neuronal protein tau is sufficient to nucleate microtubule bundles. We show that, under conditions of macro-molecular crowding, tau forms liquid-like drops. Tubulin partitions into these drops, efficiently increasing tubulin concentration and driving the nucleation of microtubules. These growing microtubules form bundles, which deform the drops while remaining enclosed by diffusible tau molecules exhibiting a liquid-like behavior. Our data suggest that condensed compartments of microtubule bundling proteins could promote the local formation of microtubule bundles in neurons by acting as non-centrosomal microtubule nucleation centers and that liquid-like tau encapsulation could provide both stability and plasticity to long axonal microtubule bundles.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Local Nucleation of Microtubule Bundles through Tubulin Concentration into a Condensed Tau Phase

et al. 2017

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“…Additional novelty of the present analysis was the demonstration of deregulated transcripts-related to cytoskeleton by DAVID categorization in the sciatic nerve of the presymptomatic ALS mice. Gene profiling in the sciatic nerve accounts for axonal (minority) and Schwann cell (majority) transcripts (Baraban et al, 2013; Malmqvist et al, 2014), thus adding an important contribution to molecular analysis on dying back hypothesis of ALS pathology (Dadon-Nachum et al, 2011; De Oliveira et al, 2014). …”

Section: Discussionmentioning

confidence: 99%

Deregulated expression of cytoskeleton related genes in the spinal cord and sciatic nerve of presymptomatic SOD1G93A Amyotrophic Lateral Sclerosis mouse model

Maximino

Oliveira

Alves

et al. 2014

Front. Cell. Neurosci.

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Early molecular events related to cytoskeleton are poorly described in Amyotrophic Lateral Sclerosis (ALS), especially in the Schwann cell (SC), which offers strong trophic support to motor neurons. Database for Annotation, Visualization and Integrated Discovery (DAVID) tool identified cytoskeleton-related genes by employing the Cellular Component Ontology (CCO) in a large gene profiling of lumbar spinal cord and sciatic nerve of presymptomatic SOD1G93A mice. One and five CCO terms related to cytoskeleton were described from the spinal cord deregulated genes of 40 days (actin cytoskeleton) and 80 days (microtubule cytoskeleton, cytoskeleton part, actin cytoskeleton, neurofilament cytoskeleton, and cytoskeleton) old transgene mice, respectively. Also, four terms were depicted from the deregulated genes of sciatic nerve of 60 days old transgenes (actin cytoskeleton, cytoskeleton part, microtubule cytoskeleton and cytoskeleton). Kif1b was the unique deregulated gene in more than one studied region or presymptomatic age. The expression of Kif1b [quantitative polymerase chain reaction (qPCR)] elevated in the lumbar spinal cord (40 days old) and decreased in the sciatic nerve (60 days old) of presymptomatic ALS mice, results that were in line to microarray findings. Upregulation (24.8 fold) of Kif1b was seen in laser microdissected enriched immunolabeled motor neurons from the spinal cord of 40 days old presymptomatic SOD1G93A mice. Furthermore, Kif1b was dowregulated in the sciatic nerve Schwann cells of presymptomatic ALS mice (60 days old) that were enriched by means of cell microdissection (6.35 fold), cell sorting (3.53 fold), and primary culture (2.70 fold) technologies. The gene regulation of cytoskeleton molecules is an important occurrence in motor neurons and Schwann cells in presymptomatic stages of ALS and may be relevant in the dying back mechanisms of neuronal death. Furthermore, a differential regulation of Kif1b in the spinal cord and sciatic nerve cells emerged as key event in ALS.

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“…Tau mRNA has a long 3 0 -UTR that contains specific elements regulating mRNA localization and stability. Several trans-acting factors that associate with the 3 0 -UTR of tau mRNA have been identified, including HuD, an embryonic lethal abnormal vision-like family protein with three RRMs, which regulates the stability of tau mRNA [10][11][12]. UV cross-linking combined with infrared imaging using the Odyssey V R system offers a convenient and robust strategy of general applicability to not only demonstrate but also characterize RNA-protein interactions.…”

Section: Introductionmentioning

confidence: 99%

A UV cross-linking method combined with infrared imaging to analyse RNA–protein interactions

Malmqvist

Spickett

Gallo

et al. 2017

Biology Methods and Protocols

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Photo cross-linking of proteins with short RNA oligomers is a classical method to study RNA-protein interactions that are implicated in many aspects of RNA metabolism and function. Most commonly, this involves the use of [c-32 P]-labeled RNA probes. Although very sensitive, these procedures are complicated by the safety issues associated with the use of radioisotopes. Here, we describe a modified UV cross-linking method using oligonucleotide probes end labelled with the infrared dye IRDyeV R 800. After UV cross-linking, proteins are separated by SDS-PAGE and cross-linked products are visualized with the Odyssey V R Infrared Imaging system. This end labelling approach provides a streamlined alternative to random labelling which reduces the efficiency of in-vitro transcription. End labelling is also independent of the length of the probe, thus facilitating quantitative comparisons. To validate the method, we have confirmed the binding of HuD to the 3 0 -UTR of the mRNA for the microtubule-associated protein tau, implicated in the pathogenesis of Alzheimer's disease. UV cross-linking of HuD with a labeled 21-mer probe was successfully performed using a recombinant purified glutathione-S-transferase-HuD fusion protein as well as with lysates from CHO cells transfected with HuD cDNA. UV cross-linking combined with infrared imaging offers a convenient and robust strategy to analyse RNA-protein interactions and their emerging importance in disease.

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Tau mRNA is present in axonal RNA granules and is associated with elongation factor 1A

Cited by 14 publications

References 17 publications

Local Nucleation of Microtubule Bundles through Tubulin Concentration into a Condensed Tau Phase

Local Nucleation of Microtubule Bundles through Tubulin Concentration into a Condensed Tau Phase

Deregulated expression of cytoskeleton related genes in the spinal cord and sciatic nerve of presymptomatic SOD1G93A Amyotrophic Lateral Sclerosis mouse model

A UV cross-linking method combined with infrared imaging to analyse RNA–protein interactions

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