Local translation in neurons: visualization and function

Nature Structural & Molecular Biology, Год журнала: 2019, Номер 26(7), С. 557 - 566

Опубликована: Июль 1, 2019

Язык: Английский

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Local protein synthesis is a ubiquitous feature of neuronal pre- and postsynaptic compartments

Science, Год журнала: 2019, Номер 364(6441)

Опубликована: Май 16, 2019

Local translation in presynaptic terminals Proteins carry out most of the functions cells, including neurons, which are one morphologically complex cell types body. This poses challenges for how proteins can be supplied to remote regions where connections (synapses) made with other neurons. One solution neuron protein-supply problem involves local synthesis from messenger RNA (mRNA) molecules located at or near synapses. Hafner et al. used sequencing methods and superresolution microscopy show that axon contain hundreds mRNA as well machinery needed protein synthesis. Furthermore, were able use these components make participate synaptic transmission. Science , this issue p. eaau3644

Язык: Английский

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Local and global influences on protein turnover in neurons and glia

eLife, Год журнала: 2018, Номер 7

Опубликована: Июнь 19, 2018

Regulation of protein turnover allows cells to react their environment and maintain homeostasis. Proteins can show different rates in tissue, but little is known about brain cell types. We used dynamic SILAC determine half-lives over 5100 proteins rat primary hippocampal cultures as well neuron-enriched glia-enriched ranging from <1 >20 days. In contrast synaptic proteins, membrane were relatively shorter-lived mitochondrial longer-lived compared the population. Half-lives also correlate with functions dynamics complexes they are incorporated in. glia possessed shorter than same neurons. The presence sped up or slowed down neuronal proteins. Our results demonstrate that both cell-type origin nature extracellular have potent influences on turnover.

Язык: Английский

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Cell-type-specific metabolic labeling of nascent proteomes in vivo

Nature Biotechnology, Год журнала: 2017, Номер 35(12), С. 1196 - 1201

Опубликована: Ноя. 6, 2017

Язык: Английский

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RNA transport and local translation in neurodevelopmental and neurodegenerative disease

Nature Neuroscience, Год журнала: 2021, Номер 24(5), С. 622 - 632

Опубликована: Янв. 28, 2021

Язык: Английский

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Keeping Your Brain in Balance: Homeostatic Regulation of Network Function

Annual Review of Neuroscience, Год журнала: 2024, Номер 47(1), С. 41 - 61

Опубликована: Фев. 21, 2024

To perform computations with the efficiency necessary for animal survival, neocortical microcircuits must be capable of reconfiguring in response to experience, while carefully regulating excitatory and inhibitory connectivity maintain stable function. This dynamic fine-tuning is accomplished through a rich array cellular homeostatic plasticity mechanisms that stabilize important network features such as firing rates, information flow, sensory tuning properties. Further, these functional properties can stabilized by different forms plasticity, including target or synapses, regulate intrinsic neuronal excitability. Here we discuss which aspects circuit function are under control, how this homeostasis realized on molecular levels, pathological consequences when impaired. A remaining challenge elucidate diverse cooperate within complex circuits enable them both flexible stable.

Язык: Английский

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Rapid Cue-Specific Remodeling of the Nascent Axonal Proteome

Neuron, Год журнала: 2018, Номер 99(1), С. 29 - 46.e4

Опубликована: Июнь 28, 2018

Axonal protein synthesis and degradation are rapidly regulated by extrinsic signals during neural wiring, but the full landscape of proteomic changes remains unknown due to limitations in axon sampling sensitivity. By combining pulsed stable isotope labeling amino acids cell culture with single-pot solid-phase-enhanced sample preparation, we characterized nascent proteome isolated retinal axons on an unparalleled rapid timescale (5 min). Our analysis detects 350 basally translated axonal proteins average, including several linked neurological disease. Axons stimulated different cues (Netrin-1, BDNF, Sema3A) show distinct signatures more than 100 species up- or downregulated within first 5 min followed further dynamic remodeling. Switching repulsion attraction triggers opposite regulation a subset common proteins. findings thus reveal remodeling uncover logic underlying versus repulsion.

Язык: Английский

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Local translation in neuronal processes

Current Opinion in Neurobiology, Год журнала: 2019, Номер 57, С. 141 - 148

Опубликована: Март 9, 2019

Язык: Английский

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The genes associated with early-onset Alzheimer’s disease

Oncotarget, Год журнала: 2017, Номер 9(19), С. 15132 - 15143

Опубликована: Дек. 15, 2017

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accounts for the most cases of dementia, which characterized by deposition dense plaques amyloid beta (Aβ) and neurofibrillary tangles consisting hyperphosphorylated tau. The two main types AD can be classified as early-onset (EOAD, onset < 65 years) late-onset (LOAD, ≥ years). Evidence from family twin studies indicate genetic factors are estimated to play role in at least 80% cases. first milestone with linkage analysis revealed mutations

Язык: Английский

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Proteome Turnover in the Spotlight: Approaches, Applications, and Perspectives

Molecular & Cellular Proteomics, Год журнала: 2020, Номер 20, С. 100016 - 100016

Опубликована: Дек. 1, 2020

In all cells, proteins are continuously synthesized and degraded to maintain protein homeostasis modify gene expression levels in response stimuli. Collectively, the processes of synthesis degradation referred as turnover. At a steady state, turnover is constant homeostasis, but dynamic responses, change their rates adjust proteomes internal or external Thus, probing kinetics dynamics lends insight into how cells regulate essential such growth, differentiation, stress response. Here, we outline historical current approaches measuring on proteome-wide scale both steady-state systems, with an emphasis metabolic tracing using stable isotope-labeled amino acids. We highlight important considerations for designing proteome experiments, key biological findings regarding conserved principles regulation, future perspectives technological investigation.

Язык: Английский

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