Single-molecule insights into mRNA dynamics in neurons

Buxbaum, Adina R.; Yoon, Yong‐Dal; Singer, Robert H.; Park, Hye Yoon

doi:10.1016/j.tcb.2015.05.005

Cited by 69 publications

(75 citation statements)

References 98 publications

(127 reference statements)

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“…In neurons, mRNAs can be trafficked to distant sites in axons and dendrites for local translation and processing [52][53][54][55][56][57]. A range of neuronal transmembrane proteins, including AMPARs, NMDARs and GABA B Rs, can be translated using both somatic and dendritically localised ribosome patterned rough ER.…”

Section: Local Dendritic Translation and Secretory Pathway Traffickingmentioning

confidence: 99%

Exciting Times: New Advances Towards Understanding the Regulation and Roles of Kainate Receptors

et al. 2017

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Kainate receptors (KARs) are glutamate-gated ion channels that play fundamental roles in regulating neuronal excitability and network function in the brain. After being cloned in the 1990s, important progress has been made in understanding the mechanisms controlling the molecular and cellular properties of KARs, and the nature and extent of their regulation of wider neuronal activity. However, there have been significant recent advances towards understanding KAR trafficking through the secretory pathway, their precise synaptic positioning, and their roles in synaptic plasticity and disease. Here we provide an overview highlighting these new findings about the mechanisms controlling KARs and how KARs, in turn, regulate other proteins and pathways to influence synaptic function.

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Section: Local Dendritic Translation and Secretory Pathway Traffickingmentioning

confidence: 99%

Exciting Times: New Advances Towards Understanding the Regulation and Roles of Kainate Receptors

et al. 2017

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“…Studies in mammalian cells have been done using transient transfection or cells from a β-actin mRNA MBS knock-in mouse (89) and a transgenic mouse expressing MCP-GFP (115). This technique has been extensively used to monitor real-time dynamics of transcription, nuclear export, and trafficking of mRNAs in live cells (reviewed in 20, 114) (Figure 1 a ). Also, recent advances in CRISPR-Cas technology have greatly facilitated genome editing (129) and RNA labeling (108) for live cell imaging.…”

Section: Techniques To Analyze Single-cell and Single-molecule Expresmentioning

confidence: 99%

Single-Cell and Single-Molecule Analysis of Gene Expression Regulation

et al. 2016

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Recent advancements in single-cell and single-molecule imaging technologies have resolved biological processes in time and space that are fundamental to understanding the regulation of gene expression. Observations of single-molecule events in their cellular context have revealed highly dynamic aspects of transcriptional and post-transcriptional control in eukaryotic cells. This approach can relate transcription with mRNA abundance and lifetimes. Another key aspect of single-cell analysis is the cell-to-cell variability among populations of cells. Definition of heterogeneity has revealed stochastic processes, determined characteristics of under-represented cell types or transitional states, and integrated cellular behaviors in the context of multicellular organisms. In this review, we discuss novel aspects of gene expression of eukaryotic cells and multicellular organisms revealed by the latest advances in single-cell and single-molecule imaging technology.

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“…Microscopic cargo movements are stochastic, bidirectional, and inhomogeneous along neurites, leading to to the hypothesis that trafficking is predominantly controlled by local pathways that signal demand for nearby cargo, rather than a centralized addressing system (Welte, 2004; Bressloff and Newby, 2009; Newby and Bressloff, 2010a; Doyle and Kiebler, 2011; Buxbaum et al, 2015). These local signals are not fully characterized, but there is evidence for multiple mechanisms including transient elevations in second-messengers like

C a^{2 +}

and ADP (Mironov, 2007; Wang and Schwarz, 2009), glutamate receptor activation (Kao et al, 2010; Buxbaum et al, 2014b), and changes in microtubule-associated proteins (Soundararajan and Bullock, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…A leading conceptual model ties together these details by proposing that local signalling and regulation of bidirectional trafficking determines the spatial distribution of cargo in neurons (Welte, 2004; Buxbaum et al, 2015). Doyle and Kiebler (2011) call this the ‘sushi belt model’.…”

Section: Introductionmentioning

confidence: 99%

Dendritic trafficking faces physiologically critical speed-precision tradeoffs

Williams

O’Donnell

Sejnowski

et al. 2016

eLife

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Nervous system function requires intracellular transport of channels, receptors, mRNAs, and other cargo throughout complex neuronal morphologies. Local signals such as synaptic input can regulate cargo trafficking, motivating the leading conceptual model of neuron-wide transport, sometimes called the ‘sushi-belt model’ (Doyle and Kiebler, 2011). Current theories and experiments are based on this model, yet its predictions are not rigorously understood. We formalized the sushi belt model mathematically, and show that it can achieve arbitrarily complex spatial distributions of cargo in reconstructed morphologies. However, the model also predicts an unavoidable, morphology dependent tradeoff between speed, precision and metabolic efficiency of cargo transport. With experimental estimates of trafficking kinetics, the model predicts delays of many hours or days for modestly accurate and efficient cargo delivery throughout a dendritic tree. These findings challenge current understanding of the efficacy of nucleus-to-synapse trafficking and may explain the prevalence of local biosynthesis in neurons.DOI: http://dx.doi.org/10.7554/eLife.20556.001

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Single-molecule insights into mRNA dynamics in neurons

Cited by 69 publications

References 98 publications

Exciting Times: New Advances Towards Understanding the Regulation and Roles of Kainate Receptors

Exciting Times: New Advances Towards Understanding the Regulation and Roles of Kainate Receptors

Single-Cell and Single-Molecule Analysis of Gene Expression Regulation

Dendritic trafficking faces physiologically critical speed-precision tradeoffs

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