mRNA transport &amp; local translation in neurons

Glock, Caspar; Heumüller, Maximilian; Schuman, Erin M.

doi:10.1016/j.conb.2017.05.005

Cited by 189 publications

(165 citation statements)

References 90 publications

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“…Recent advances in single mRNA imaging techniques have revealed a number of fine details about RNP transport in dendrites (Glock et al, 2017). Single-molecule fluorescence in situ hybridization (smFISH) revealed that, in dendrites, β-actin mRNA in RNA granules is sterically masked from the translation machinery as well as FISH probes, and unmasked by neuronal activity (Buxbaum et al, 2014).…”

Section: Protein Synthesis-dependent Remodeling Of the Spinementioning

confidence: 99%

Plasticity of Spine Structure: Local Signaling, Translation and Cytoskeletal Reorganization

Nakahata

Yasuda

2018

Front. Synaptic Neurosci.

177

161

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Dendritic spines are small protrusive structures on dendritic surfaces, and function as postsynaptic compartments for excitatory synapses. Plasticity of spine structure is associated with many forms of long-term neuronal plasticity, learning and memory. Inside these small dendritic compartments, biochemical states and protein-protein interactions are dynamically modulated by synaptic activity, leading to the regulation of protein synthesis and reorganization of cytoskeletal architecture. This in turn causes plasticity of structure and function of the spine. Technical advances in monitoring molecular behaviors in single dendritic spines have revealed that each signaling pathway is differently regulated across multiple spatiotemporal domains. The spatial pattern of signaling activity expands from a single spine to the nearby dendritic area, dendritic branch and the nucleus, regulating different cellular events at each spatial scale. Temporally, biochemical events are typically triggered by short Ca2+ pulses (~10–100 ms). However, these signals can then trigger activation of downstream protein cascades that can last from milliseconds to hours. Recent imaging studies provide many insights into the biochemical processes governing signaling events of molecular assemblies at different spatial localizations. Here, we highlight recent findings of signaling dynamics during synaptic plasticity and discuss their roles in long-term structural plasticity of dendritic spines.

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Section: Protein Synthesis-dependent Remodeling Of the Spinementioning

confidence: 99%

Plasticity of Spine Structure: Local Signaling, Translation and Cytoskeletal Reorganization

Nakahata

Yasuda

2018

Front. Synaptic Neurosci.

177

161

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“…This mechanism requires the presence of mRNAs, translation machinery (ribosomes and translation factors), and activation of signaling pathways upstream of translation [17]. Studies in the central and peripheral nervous systems (CNS and PNS, respectively) demonstrate that these components are present in axonal (predominantly in the PNS) and dendritic compartments (predominantly in the CNS), where they support activity-dependent protein synthesis to modify the local proteome in response to a multitude of extracellular and intracellular stimuli (reviewed in [18]).…”

Section: The Basics Of Translational Controlmentioning

confidence: 99%

“…mRNAs, ribosomes, and other components of translational machinery are present in PNS axonal and CNS dendritic compartments [17,35,36]. Release of endogenous molecules associated with tissue damage increases nascent protein synthesis in DRG neurons and their axons via activation of signaling pathways upstream of translation (Figure 3).…”

Section: Local Mrna Translationmentioning

confidence: 99%

Translational Control Mechanisms in Persistent Pain

Khoutorsky

Price

2018

Trends in Neurosciences

114

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Persistent pain, which is poorly treated and estimated to afflict one third of the world’s population, is largely mediated by the sensitization of nociceptive neurons. This sensitization involves de novo gene expression to support biochemical and structural changes required to maintain amplified pain signaling that frequently persists even after injury to tissue resolves. While transcription-dependent changes in gene expression are important, recent work demonstrates that activity-dependent regulation of mRNA translation is key to controlling the cellular proteome and the development and maintenance of persistent pain. In this review, we highlight recent advances in translational regulation of gene expression in nociceptive circuits, with a focus on key signaling pathways and mRNA targets that may be tractable for the creation of next-generation pain therapeutics.

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“…The stability of mRNA determines how much protein is synthesized from a given transcript. Especially in neurons, mRNAs are bound by RNA‐binding proteins (RBPs), and the so‐called RNA granula made of RNA and associated proteins are transported to synaptic regions . In synapses, these mRNAs can be translated directly where the protein will be required and influence synaptic plasticity .…”

Section: Main Textmentioning

confidence: 99%

Initiated by CREB: Resolving Gene Regulatory Programs in Learning and Memory

Kaldun

Sprecher

2019

BioEssays

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Consolidation of long‐term memory is a highly and precisely regulated multistep process. The transcription regulator cAMP response element‐binding protein (CREB) plays a key role in initiating memory consolidation. With time processing, first the cofactors are changed and, secondly, CREB gets dispensable. This ultimately changes the expressed gene program to genes required to maintain the memory. Regulation of memory consolidation also requires epigenetic mechanisms and control at the RNA level. At the neuronal circuit level, oscillation in the activity of CREB and downstream factor define engram cells. Together the combination of all regulation mechanisms allows correct memory processing while keeping the process dynamic and flexible to adjust to different contexts. Also see the video abstract here https://youtu.be/BhSCSmorpEc.

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mRNA transport & local translation in neurons

Cited by 189 publications

References 90 publications

Plasticity of Spine Structure: Local Signaling, Translation and Cytoskeletal Reorganization

Plasticity of Spine Structure: Local Signaling, Translation and Cytoskeletal Reorganization

Translational Control Mechanisms in Persistent Pain

Initiated by CREB: Resolving Gene Regulatory Programs in Learning and Memory

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