Real‐time imaging reveals defects of fast axonal transport induced by disorganization of intermediate filaments

Perrot, Rodolphe; Julien, Jean‐Pierre

doi:10.1096/fj.09-129585

Cited by 48 publications

(50 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Similar observations have been made by Broadwell and Cataldo [35] in pituitary axons of the human brain, and in hippocampal pyramidal cells [36] Ctr. 24 and in dorsal root ganglia [37]. Recent data of Hernandez et al [38] showed that induction of neuronal autophagy by using Rapamycin acutely increased AV-formation in presynaptic terminals, decreased the amount of synaptic vesicles and depressed evoked neurotransmitter release.…”

Section: Discussionmentioning

confidence: 99%

Axonal Accumulation of Lysosomal-Associated Membrane Protein 1 (LAMP1) Accompanying Alterations of Autophagy Dynamics in the Rat Hippocampus Upon Seizure-Induced Injury

et al. 2015

View full text Add to dashboard Cite

We found a dramatic upregulation in the expression of LC3 in the hippocampus of rats upon status epilepticus (SE). However, the enhancement in LC3 expression might be caused by a reduction in lysosomal activity or by alterations in autophagosome-lysosome fusion leading to a cytosolic vesicular retention. In order to dissect this aspect, we monitored the spatial and temporal expression of LC3 and LAMP1 in the hippocampus of rats with SE. The Western blot analysis showed that the expression of LAMP1 was slightly increased in hippocampal cells at 6, 24, and 48 h post-SE. However, immunofluorescence analysis showed dramatic spatial changes in LAMP1 distribution within the hippocampus. LAMP1 in controls was localised only in cytosol as dot like staining, however at 24 h post-SE LAMP1 was not only highly expressed, but accumulated in mossy fibers of dentate gyrus. In parallel, we found few scattered LC3-positive-dots in neurites of dentate gyrus which co-localise with LAMP1-positive structures. We conclude that SE not only increased autophagosomal abundance, but also lysosomal activities and a massive accumulation of LAMP1 in axons of dentate gyrus. This could support the hypothesis that the marked increased autophagosomal abundance in cytosol reflects an increase in the autophagic activity more than an inhibition of autophagosomal clearance. Although LAMP1 may have contributed to cell damage in the selective vulnerable hippocampal CA1-subfield, it is also possible that lysosomal/autophagic mechanisms in mossy fibers were compensatory and reflected an attempt to survive the epileptic insult by breaking down non-essential components.

show abstract

Section: Discussionmentioning

confidence: 99%

Axonal Accumulation of Lysosomal-Associated Membrane Protein 1 (LAMP1) Accompanying Alterations of Autophagy Dynamics in the Rat Hippocampus Upon Seizure-Induced Injury

et al. 2015

View full text Add to dashboard Cite

show abstract

“…IFs also impact subcellular organelles other than mitochondria. For example, the positioning, sorting or movement of lysosomes or the crosstalk between lysosomes and endosomes is impacted by vimentin [114] desmin [71], and NF [119]; and vimentin and keratins are important for the transport of melanosomes [120, 121]. Furthermore, nuclear lamin A mutations cause a variety of organelle phenotypes, such as enlarged rough endoplasmic reticulum and mitochondria in mice, and gap junctional protein mislocalization in myocytes [122].…”

Section: Involvement Of Ifs In Specific Stress Contextsmentioning

confidence: 99%

Intermediate filaments take the heat as stress proteins

Toivola¹,

Strnad²,

Habtezion³

et al. 2010

Trends in Cell Biology

244

197

View full text Add to dashboard Cite

Intermediate filament (IF) proteins and heat shock proteins (HSPs) are large multi-membered families that share several features. These features include protein abundance, significant upregulation in response to a variety of stresses, function as cytoprotectors, and the phenocopying of several human diseases upon IF protein or HSP mutation. We are now coming to understand that these common elements point to IFs as important cellular stress proteins with some roles akin to those already well-characterized for HSPs. Unique functional roles for IFs include protection from mechanical stress while HSPs are characteristically involved in protein folding and as chaperones. Shared IF and HSP cytoprotective roles include inhibition of apoptosis, organelle homeostasis, and scaffolding. We review here recent data that corroborate the view that IFs function as highlyspecialized cytoskeletal stress proteins that promote cellular organization and homeostasis. The stress responseTissues and cells are constantly subjected to stressful situations, meaning that components of the cell, including proteins, organelles and DNA, can be damaged. These stresses are both intrinsic, such as genetic and endoplasmic reticulum stress, and extrinsic/environmental stresses including heat, toxin or radiation, mechanical, wound and regenerative, infection, metabolic such as hypoxia and autophagy, osmotic and oxidative (Fig.1). The prototype response to stress, the heat stress response (HSR) is the best characterized and occurs via activation of heat shock transcription factors (HSFs), which drive the expression of multiple target genes containing the heat shock elements (HSEs) within their promoter sequence [1]. The heat shock proteins (HSPs) are the classical HSR targets and constitute a large family of proteins that are expressed constitutively and in response to stress [2] (Box 1). HSPs act as molecular chaperones assisting with normal folding, transport, and degradation of proteins and have an established stress-protective function, which extends far beyond the heat response [3,4] Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. The importance of keratins in stress-signal transmission may occur at focal adhesions since the viscoelastic response of keratin-null rat hepatoma cells is reduced, as compared with K8-or K18-containing cells, when measured using fibronectin-coated polystyrene beads and mechanical stress generated by optical tweezers [57]. Whether shear stress affects IF expression has not been studied in detail, although stretch induces K6 and decreases K10 expression [49,58]. Mechanic...

show abstract

“…Evidence is also emerging that the cytoskeleton, and especially the NF scaffold, acts as a docking platform to organize the topography of organelles within different neuronal compartments. Rearrangements of this topography are dynamically coordinated at least in part by cellular signals regulating the phosphorylation state of the binding partners [137, 143, 163, 193]. Such evidence suggests a range of possibilities for understanding the newly recognized roles of individual NF subunits in modulating synaptic function.…”

Section: Introductionmentioning

confidence: 99%

Specialized roles of neurofilament proteins in synapses: Relevance to neuropsychiatric disorders

Yuan

Nixon

2016

Brain Research Bulletin

View full text Add to dashboard Cite

Neurofilaments are uniquely complex among classes of intermediate filaments in being composed of four subunits (NFL, NFM, NFH and alpha-internexin in the CNS) that differ in structure, regulation, and function. Although neurofilaments have been traditionally viewed as axonal structural components, recent evidence has revealed that distinctive assemblies of neurofilament subunits are integral components of synapses, especially at postsynaptic sites. Within the synaptic compartment, the individual subunits differentially modulate neurotransmission and behavior through interactions with specific neurotransmitter receptors. These newly uncovered functions suggest that alterations of neurofilament proteins not only underlie axonopathy in various neurological disorders but also may play vital roles in cognition and neuropsychiatric diseases. Here, we review evidence that synaptic neurofilament proteins are a sizable population in the CNS and we advance the concept that changes in the levels or post-translational modification of individual NF subunits contribute to synaptic and behavioral dysfunction in certain neuropsychiatric conditions.

show abstract

Real‐time imaging reveals defects of fast axonal transport induced by disorganization of intermediate filaments

Cited by 48 publications

References 53 publications

Axonal Accumulation of Lysosomal-Associated Membrane Protein 1 (LAMP1) Accompanying Alterations of Autophagy Dynamics in the Rat Hippocampus Upon Seizure-Induced Injury

Axonal Accumulation of Lysosomal-Associated Membrane Protein 1 (LAMP1) Accompanying Alterations of Autophagy Dynamics in the Rat Hippocampus Upon Seizure-Induced Injury

Intermediate filaments take the heat as stress proteins

Specialized roles of neurofilament proteins in synapses: Relevance to neuropsychiatric disorders

Contact Info

Product

Resources

About