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Identification of synaptoneurosomal transcriptome engaged into translation in response to NMDA-R stimulation

ABSTRACT: Synapses are the regions of the neuron that enable the transmission and propagation of action potentials on the cost of high energy consumption and elevated demand for mitochondrial ATP production. The rapid changes in local energetic requirements at dendritic spines implies the role of mitochondria in the maintenance of their homeostasis. We have employed quantitative mass spectrometry and in vitro stimulation of isolated mouse synaptoneurosomes to create a comprehensive view of local protein synthesis in neurons. Strikingly, the second most numerus group of proteins synthetized in the synapses represented ones imported into the mitochondria. The proteomic data were further supported by sequencing of mRNAs bound with actively translating polyribosomes. Our results show that an important pool of mitochondrial proteins is locally produced at the synapse indicting that mitochondrial biogenesis take place locally in order to maintain the pool of functional mitochondria in axons and dendrites. We further show that stimulation of synaptoneurosomes induce the local synthesis of mitochondrial proteins that are transported to the mitochondria and incorporated into the protein supercomplexes of respiratory chain. This contributes to mitochondrial biogenesis in neurons and a logical consequence of this fact would be a dysregulation of mitochondrial function in the conditions that deal with dysregulated synaptic translation, such as fragile X syndrome. Indeed, we have shown mitochondrial dysfunction in synapses of Fmr1 KO mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE122724 | GEO | 2020/04/14

REPOSITORIES: GEO

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VAP spatially stabilizes dendritic mitochondria to locally support synaptic plasticity

Project description:Synapses are pivotal sites of plasticity and memory formation. Consequently, synapses are energy consumption hotspots susceptible to dysfunction when their energy supplies are perturbed. Mitochondria are stabilized near synapses via the cytoskeleton and provide the local energy required for synaptic plasticity. However, the mechanisms that tether and stabilize mitochondria to support synaptic plasticity are unknown. We identified proteins exclusively tethering mitochondria to actin near postsynaptic spines. We find that VAP, the vesicle-associated membrane protein-associated protein implicated in amyotrophic lateral sclerosis, stabilizes mitochondria via actin near the spines. To test if the VAP-dependent stable mitochondrial compartments can locally support synaptic plasticity, we used two-photon glutamate uncaging for spine plasticity induction and investigated the induced and adjacent uninduced spines. We find VAP functions as a spatial stabilizer of mitochondrial compartments for up to ~60 min and as a spatial ruler determining the ~30 m dendritic segment supported during synaptic plasticity.

2023-11-27 | PXD047226 | Pride

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Neuronal ribosomes dynamically exchange ribosomal proteins in a context-dependent manner.

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RNA-seq transcriptional profiling in human primary fetal and adult CD34+ hematopoietic stem/progenitor cells (HSPCs) erythroid progenitor cells (ProEs)

2017-05-15 | GSE74053 | GEO

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Gene expression analysis in 13 patients with mitochondrial ATP synthase deficiency (MitoArray)

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