Slow axoplasmic transport under scrutiny

Court, Felipe A.; Álvarez, Jaime

doi:10.4067/s0716-97602011000400001

Cited by 8 publications

(4 citation statements)

References 95 publications

(77 reference statements)

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“…Local translation circumvents undesired protein activities during long‐haul transport (reviewed in Ref. ), and is validated by the decaying time of proteins during vesicular transport, which may constitute a limiting factor in neurons . Indeed, it may take far longer than the half‐life of a protein to reach their destination via transport, as only 10% of the proteins synthesized in the soma, measured by radioactive labeling, reach the axon terminal …”

Section: Local Protein Synthesis and Trafficking In The Axonmentioning

confidence: 99%

Global and local mechanisms sustain axonal proteostasis of transmembrane proteins

Cornejo

Luarte

Couve

2017

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The control of neuronal protein homeostasis or is tightly regulated both spatially and temporally, assuring accurate and integrated responses to external or intrinsic stimuli. Local or autonomous responses in dendritic and axonal compartments are crucial to sustain function during development, physiology and in response to damage or disease. Axons are responsible for generating and propagating electrical impulses in neurons, and the establishment and maintenance of their molecular composition are subject to extreme constraints exerted by length and size. Proteins that require the secretory pathway, such as receptors, transporters, ion channels or cell adhesion molecules, are fundamental for axonal function, but whether axons regulate their abundance autonomously and how they achieve this is not clear. Evidence supports the role of three complementary mechanisms to maintain proteostasis of these axonal proteins, namely vesicular transport, local translation and trafficking and transfer from supporting cells. Here, we review these mechanisms, their molecular machineries and contribution to neuronal function. We also examine the signaling pathways involved in local translation and their role during development and nerve injury. We discuss the relative contributions of a transport-controlled proteome directed by the soma (global regulation) versus a local-controlled proteome based on local translation or cell transfer (local regulation).

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Section: Local Protein Synthesis and Trafficking In The Axonmentioning

confidence: 99%

Global and local mechanisms sustain axonal proteostasis of transmembrane proteins

Cornejo

Luarte

Couve

2017

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“…However, energetic and temporal considerations suggest that transport may not be sufficient to control the immediate requirements of the distal proteome, especially under conditions of regeneration (3). Localization of mRNA and de novo protein synthesis provide an alternative to respond quickly to local demands (4).…”

mentioning

confidence: 99%

Axons provide the secretory machinery for trafficking of voltage-gated sodium channels in peripheral nerve

González

Cánovas

Fresno

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The regulation of the axonal proteome is key to generate and maintain neural function. Fast and slow axoplasmic waves have been known for decades, but alternative mechanisms to control the abundance of axonal proteins based on local synthesis have also been identified. The presence of the endoplasmic reticulum has been documented in peripheral axons, but it is still unknown whether this localized organelle participates in the delivery of axonal membrane proteins. Voltage-gated sodium channels are responsible for action potentials and are mostly concentrated in the axon initial segment and nodes of Ranvier. Despite their fundamental role, little is known about the intracellular trafficking mechanisms that govern their availability in mature axons. Here we describe the secretory machinery in axons and its contribution to plasma membrane delivery of sodium channels. The distribution of axonal secretory components was evaluated in axons of the sciatic nerve and in spinal nerve axons after in vivo electroporation. Intracellular protein trafficking was pharmacologically blocked in vivo and in vitro. Axonal voltage-gated sodium channel mRNA and local trafficking were examined by RT-PCR and a retentionrelease methodology. We demonstrate that mature axons contain components of the endoplasmic reticulum and other biosynthetic organelles. Axonal organelles and sodium channel localization are sensitive to local blockade of the endoplasmic reticulum to Golgi transport. More importantly, secretory organelles are capable of delivering sodium channels to the plasma membrane in isolated axons, demonstrating an intrinsic capacity of the axonal biosynthetic route in regulating the axonal proteome in mammalian axons.axon | endoplasmic reticulum | trafficking

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“…Furthermore, in vivo experiments have shown that SMN directly modulates a specific subset of ribosomes implicated in the translation of mRNAs related to ribosome biogenesis, bioenergetics, and neuronal function [ 45 ]. Ribosomes have been identified at motor nerve terminals by immunoelectron and conventional electron microscopy [ 57 , 58 ]. To check for the presence of ribosomes at the presynaptic motor terminal of control and SMA SMNΔ7 mice, we performed a transmission EM study and investigated the distribution of ribosomes and polysomes, according to the criteria of these previous studies.…”

Section: Resultsmentioning

confidence: 99%

SMN Is Physiologically Downregulated at Wild-Type Motor Nerve Terminals but Aggregates Together with Neurofilaments in SMA Mouse Models

et al. 2022

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Survival motor neuron (SMN) is an essential and ubiquitously expressed protein that participates in several aspects of RNA metabolism. SMN deficiency causes a devastating motor neuron disease called spinal muscular atrophy (SMA). SMN forms the core of a protein complex localized at the cytoplasm and nuclear gems and that catalyzes spliceosomal snRNP particle synthesis. In cultured motor neurons, SMN is also present in dendrites and axons, and forms part of the ribonucleoprotein transport granules implicated in mRNA trafficking and local translation. Nevertheless, the distribution, regulation, and role of SMN at the axons and presynaptic motor terminals in vivo are still unclear. By using conventional confocal microscopy and STED super-resolution nanoscopy, we found that SMN appears in the form of granules distributed along motor axons at nerve terminals. Our fluorescence in situ hybridization and electron microscopy studies also confirmed the presence of β-actin mRNA, ribosomes, and polysomes in the presynaptic motor terminal, key elements of the protein synthesis machinery involved in local translation in this compartment. SMN granules co-localize with the microtubule-associated protein 1B (MAP1B) and neurofilaments, suggesting that the cytoskeleton participates in transporting and positioning the granules. We also found that, while SMN granules are physiologically downregulated at the presynaptic element during the period of postnatal maturation in wild-type (non-transgenic) mice, they accumulate in areas of neurofilament aggregation in SMA mice, suggesting that the high expression of SMN at the NMJ, together with the cytoskeletal defects, contribute to impairing the bi-directional traffic of proteins and organelles between the axon and the presynaptic terminal.

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Slow axoplasmic transport under scrutiny

Cited by 8 publications

References 95 publications

Global and local mechanisms sustain axonal proteostasis of transmembrane proteins

Global and local mechanisms sustain axonal proteostasis of transmembrane proteins

Axons provide the secretory machinery for trafficking of voltage-gated sodium channels in peripheral nerve

SMN Is Physiologically Downregulated at Wild-Type Motor Nerve Terminals but Aggregates Together with Neurofilaments in SMA Mouse Models

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