Synapse-specific burst coding sustained by local axonal translation DOI Creative Commons
Hovy Ho‐Wai Wong, Alanna J. Watt, P. Jesper Sjöström

и другие.

Neuron, Год журнала: 2023, Номер 112(2), С. 264 - 276.e6

Опубликована: Ноя. 8, 2023

Neurotransmission in the brain is unreliable, suggesting that high-frequency spike bursts rather than individual spikes carry neural code. For instance, cortical pyramidal neurons rely on memory formation. Protein synthesis another key factor long-term synaptic plasticity and learning but widely considered unnecessary for transmission. Here, however, we show burst neurotransmission at synapses between neocortical layer 5 cells depends axonal protein linked to presynaptic NMDA receptors mTOR. We localized axons with laser axotomy puromycylation live imaging. whole-cell recorded connected reveal how translation sustained readily releasable vesicle pool size replenishment rate. imaged found sparsely docked RNA granules, synapse-specific regulation. In agreement, boosted onto excitatory not inhibitory basket or Martinotti cells. Local mRNA thus a hitherto unappreciated principle sustaining coding specific synapse types.

Язык: Английский

Single-pot, solid-phase-enhanced sample preparation for proteomics experiments DOI
Christopher S. Hughes, Sophie Moggridge,

Torsten Müller

и другие.

Nature Protocols, Год журнала: 2018, Номер 14(1), С. 68 - 85

Опубликована: Ноя. 16, 2018

Язык: Английский

Процитировано

1345
Local translation in neurons: visualization and function DOI
Christine E. Holt, Kelsey C. Martin,

Erin M. Schuman

и другие.

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

Опубликована: Июль 1, 2019

Язык: Английский

Процитировано

463
R2‐P2 rapid‐robotic phosphoproteomics enables multidimensional cell signaling studies DOI Creative Commons
Mario Leutert, Ricard A. Rodríguez‐Mias, Noelle K. Fukuda

и другие.

Molecular Systems Biology, Год журнала: 2019, Номер 15(12)

Опубликована: Дек. 1, 2019

Recent developments in proteomics have enabled signaling studies where > 10,000 phosphosites can be routinely identified and quantified. Yet, current analyses are limited throughput, reproducibility, robustness, hampering experiments that involve multiple perturbations, such as those needed to map kinase-substrate relationships, capture pathway crosstalks, network inference analysis. To address these challenges, we introduce rapid-robotic phosphoproteomics (R2-P2), an end-to-end automated method uses magnetic particles process protein extracts deliver mass spectrometry-ready phosphopeptides. R2-P2 is rapid, robust, versatile, high-throughput. showcase the method, applied it, combination with data-independent acquisition spectrometry, study dynamics mitogen-activated kinase (MAPK) yeast. Our results reveal broad specific events along mating, high-osmolarity glycerol, invasive growth branches of MAPK pathway, robust phosphorylation downstream regulatory proteins transcription factors. facilitates large-scale involving hundreds perturbations opening door systems-level aiming complexity.

Язык: Английский

Процитировано

158
RNA transport and local translation in neurodevelopmental and neurodegenerative disease DOI
Michael S. Fernandopulle, Jennifer Lippincott‐Schwartz, Michael E. Ward

и другие.

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

Опубликована: Янв. 28, 2021

Язык: Английский

Процитировано

140
On-Site Ribosome Remodeling by Locally Synthesized Ribosomal Proteins in Axons DOI Creative Commons
Toshiaki Shigeoka, Max Koppers, Hovy Ho‐Wai Wong

и другие.

Cell Reports, Год журнала: 2019, Номер 29(11), С. 3605 - 3619.e10

Опубликована: Дек. 1, 2019

Ribosome assembly occurs mainly in the nucleolus, yet recent studies have revealed robust enrichment and translation of mRNAs encoding many ribosomal proteins (RPs) axons, far away from neuronal cell bodies. Here, we report a physical functional interaction between locally synthesized RPs ribosomes axon. We show that axonal RP is regulated through sequence motif, CUIC, forms an RNA-loop structure region immediately upstream initiation codon. Using imaging subcellular proteomics techniques, axons join nucleolus-independent fashion. Inhibition CUIC-regulated decreases local activity reduces axon branching developing brain, revealing physiological relevance synthesis vivo. These results suggest supplies cytoplasmic to maintain/modify function nucleolus neurons.

Язык: Английский

Процитировано

143
Genetic Convergence Brings Clarity to the Enigmatic Red Line in ALS DOI Creative Commons
Casey Cook, Leonard Petrucelli

Neuron, Год журнала: 2019, Номер 101(6), С. 1057 - 1069

Опубликована: Март 1, 2019

Язык: Английский

Процитировано

125
Disease-modifying therapies in amyotrophic lateral sclerosis DOI
Adriano Chiò, Letizia Mazzini, Gabriele Mora

и другие.

Neuropharmacology, Год журнала: 2020, Номер 167, С. 107986 - 107986

Опубликована: Фев. 3, 2020

Язык: Английский

Процитировано

100
Noncanonical Modulation of the eIF2 Pathway Controls an Increase in Local Translation during Neural Wiring DOI Creative Commons

Roberta Cagnetta,

Hovy Ho‐Wai Wong, Christian K. Frese

и другие.

Molecular Cell, Год журнала: 2018, Номер 73(3), С. 474 - 489.e5

Опубликована: Дек. 27, 2018

Local translation is rapidly regulated by extrinsic signals during neural wiring, but its control mechanisms remain elusive. Here we show that the extracellular cue Sema3A induces an initial burst in local precisely controls phosphorylation of initiation factor eIF2α via unfolded protein response (UPR) kinase PERK. Strikingly, contrast to canonical UPR signaling, Sema3A-induced bypasses global translational repression and underlies increase through differential activity eIF2B mediated phosphatase 1. Ultrasensitive proteomics analysis axons reveals 75 proteins translationally controlled Sema3A-p-eIF2α pathway. These include proteostasis- actin cytoskeleton-related not stress markers. Finally, PERK signaling needed for directional axon migration visual pathway development vivo. Thus, our findings reveal a noncanonical eIF2 selective changes required wiring.

Язык: Английский

Процитировано

96
Neuronal ribonucleoprotein granules: Dynamic sensors of localized signals DOI Open Access
Nadia Formicola, Jeshlee Vijayakumar, Florence Besse

и другие.

Traffic, Год журнала: 2019, Номер 20(9), С. 639 - 649

Опубликована: Июнь 17, 2019

Abstract Membrane‐less organelles, because of their capacity to dynamically, selectively and reversibly concentrate molecules, are very well adapted for local information processing rapid response environmental fluctuations. These features particularly important in the context neuronal cells, where synapse‐specific activation, or localized extracellular cues, induce signaling events restricted specialized axonal dendritic subcompartments. Neuronal ribonucleoprotein (RNP) particles, granules, nonmembrane bound macromolecular condensates that specific sets mRNAs regulatory proteins, promoting long‐distance transport axons dendrites. RNP granules also have a dual function regulating translation associated mRNAs: while preventing mRNA at rest, they fuel protein synthesis upon activation. As revealed by recent work, reversible switches between these two functional modes triggered modifications networks interactions underlying granule assembly. Such flexible properties come with cost, as prone transition into pathological aggregates mutations, aging, cellular stresses, further emphasizing need better understand mechanistic principles governing dynamic assembly regulation living systems.

Язык: Английский

Процитировано

81
RNA-binding proteins balance brain function in health and disease DOI Creative Commons
Rico Schieweck, Jovica Ninkovic, Michael Kiebler

и другие.

Physiological Reviews, Год журнала: 2020, Номер 101(3), С. 1309 - 1370

Опубликована: Окт. 1, 2020

Posttranscriptional gene expression including splicing, RNA transport, translation, and decay provides an important regulatory layer in many if not all molecular pathways. Research the last decades has positioned RNA-binding proteins (RBPs) right center of posttranscriptional regulation. Here, we propose interdependent networks RBPs to regulate complex pathways within central nervous system (CNS). These are involved multiple aspects neuronal development functioning, higher cognition. Therefore, it is sufficient unravel individual contribution a single RBP its consequences but rather study understand tight interplay between different RBPs. In this review, summarize recent findings field biology discuss Second, emphasize underlying dynamics network how might key processes such as neurogenesis, synaptic transmission, plasticity. Importantly, envision that dysfunction specific could lead perturbation network. This would have direct indirect (compensatory) effects mRNA binding translational control leading global changes cellular programs general plasticity particular. focus on cause neuropsychiatric neurodegenerative disorders. Based findings, alterations entire account for phenotypic dysfunctions observed diseases neurodegeneration, epilepsy, autism spectrum

Язык: Английский

Процитировано

81