Intermediate filaments and cellular mechanics

Goldmann, Wolfgang H.

doi:10.1002/cbin.10879

Cited by 44 publications

(41 citation statements)

References 43 publications

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“…Our model system did not include mechanical load, a force which plectin allows cells to respond to 18 , 19 , 20 . Aberrant mechanical load, including only moderate change, can elicit an inflammatory response that has been termed “mechanoflammation” 42 .…”

Section: Discussionmentioning

confidence: 99%

“…PLEC encodes plectin, a large cytoskeletal protein that regulates signalling from the extracellular environment to the cell nucleus 18 , 19 . Plectin enables cells to respond to external mechanical stimuli and forces, such as those experienced by the chondrocyte during joint movement 20 . Although cartilage loss is central to the OA disease process, there are pathological changes to other tissues of the articulating joint that occur concurrent to and following the loss of cartilage 21 .…”

Section: Introductionmentioning

confidence: 99%

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Multi-tissue epigenetic analysis of the osteoarthritis susceptibility locus mapping to the plectin gene PLEC

Sorial

Hofer

Tselepi

et al. 2020

Osteoarthritis and Cartilage

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Summary Objective In cartilage, the osteoarthritis (OA) associated single nucleotide polymorphism (SNP) rs11780978 correlates with differential expression of PLEC , and with differential methylation of PLEC CpG dinucleotides, forming eQTLs and mQTLs respectively. This implies that methylation links chondrocyte genotype and phenotype, thus driving the functional effect of this genetic risk signal. PLEC encodes plectin, a cytoskeletal protein that enables tissues to respond to mechanical forces. We sought to assess whether these PLEC functional effects were cartilage specific. Method Cartilage, fat pad, synovium and peripheral blood were collected from patients undergoing arthroplasty. PLEC CpGs were analysed for mQTLs and allelic expression imbalance (AEI) was performed to test for eQTLs. Plectin was knocked down in a mesenchymal stem cell (MSC) line using CRISPR/Cas9 and cells phenotyped by RNA-sequencing. Results mQTLs were discovered in fat pad, synovium and blood. Their effects were however stronger in the joint tissues and of comparable effect between these tissues. We observed AEI in synovium in the same direction as for cartilage and correlations between methylation and PLEC expression. Knocking-down plectin impacted on pathways reported to have a role in OA, including Wnt signalling, glycosaminoglycan biosynthesis and immune regulation. Conclusions Synovium is also a target of the rs11780978 OA association functionally operating on PLEC . In fat pad, mQTLs were identified but these did not correlate with PLEC expression, suggesting the functional effect is not joint-wide. Our study highlights interplay between genetic risk, DNA methylation and gene expression in OA, and reveals clear differences between tissues from the same diseased joint.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Multi-tissue epigenetic analysis of the osteoarthritis susceptibility locus mapping to the plectin gene PLEC

Sorial

Hofer

Tselepi

et al. 2020

Osteoarthritis and Cartilage

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“…infecting muscles of various decapods (for reference see (Small et al 2019;Stentiford et al 2013), as well as in Areospora rohanae (Stentiford et al 2014). At the first glance their fine morphology does not match the one of any kind of intermediate filaments conventionally organized in 7-10 nm thick bundles (Goldmann 2018;Marceau et al 2014;Melcer et al 2007). However, ultrastructural examinations of isolated spores of A. michaelis rinsed in distilled water before fixation in osmium tetroxide), reveals a canopy of filament bundles about 7 nm each composed of even thinner proto-filament-like structures (Fig.…”

Section: Filamentous Structures Revealed On the Surface Of Microsporimentioning

confidence: 99%

Microsporidia Can Acquire Lamin‐like Intermediate Filaments and Cell Adhesion Catenin‐cadherin Complexes from the Host (?)

Weidner

Sokolova

Overstreet

2020

J Eukaryotic Microbiology

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On their spore surfaces, Microsporidia often develop a canopy of filaments with characteristics of intermediate filaments (IF), as we demonstrated in previous studies on Thelohania sp., Ameson michaelis, and Spraguea lophii. Genomic studies indicate that among invertebrates, lamins that may localize in the cytoplasm or nucleus, are the only known IF type. These IFs can bind to the substrate containing cell adhesion molecules (CAMs) cadherins, associated with β and γ catenins. The objects of this study were to determine whether microsporidia have CAMs with the attached IFs on their envelopes and to find out if these proteins are provided by the host. An examination was made for localization of lamins and CAMs on the spores of the mentioned above species and Anncaliia algerae, plus in the host animals. Then, we determined whether the spores of A. michaelis and A. algerae could bind vertebrate nuclear lamin onto the spore surface. We also tested transgenic Drosophila melanogaster stocks bearing cadherin‐GFP to see whether developing A. algerae parasites in these hosts could acquire host CAMs. The tests were positive for all these experiments. We hypothesize that microsporidia are able to acquire host lamin IFs and cell adhesion catenin–cadherin complexes from the host.

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“…Intermediate filaments (IFs) provide mechanical strength to cells and mediate the formation of tissues (Coulombe & Wong, ; Goldmann, ). Perhaps nowhere can the need for long‐term, mechanical support be more critical than in axons, which once synaptogenesis has occurred, remain in place for the lifetime of the individual.…”

Section: Introductionmentioning

confidence: 99%

Neurofilaments form flexible bundles during neuritogenesis in culture and in mature axons in situ

Lee

Eyer²,

Letournel

et al. 2019

J of Neuroscience Research

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Neurofilaments (NFs) undergo cation-dependent phospho-mediated associationswith each other and other cytoskeletal elements that support axonal outgrowth.Progressive NF-NF associations generate a resident, bundled population that undergoes exchange with transporting NFs. We examined the properties of bundled NFs.Bundles did not always display a fully linear profile but curved and twisted at various points along the neurite length. Bundles retracted faster than neurites and retracted bundles did not expand following extraction with Triton, indicating that they coiled passively rather than due to pressure from the cell. Bundles consisted of helically wound NFs, which may provide flexibility necessary for turning of growing axons during pathfinding. Interactions between NFs and other cytoskeletal elements may be disrupted en masse during neurite retraction or regionally during remodeling. It is suggested that bundles within long axons that cannot be fully retracted into the soma could provide maintain proximal support yet still allow more distal flexibility for remodeling and changing direction during pathfinding.

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Intermediate filaments and cellular mechanics

Cited by 44 publications

References 43 publications

Multi-tissue epigenetic analysis of the osteoarthritis susceptibility locus mapping to the plectin gene PLEC

Multi-tissue epigenetic analysis of the osteoarthritis susceptibility locus mapping to the plectin gene PLEC

Microsporidia Can Acquire Lamin‐like Intermediate Filaments and Cell Adhesion Catenin‐cadherin Complexes from the Host (?)

Neurofilaments form flexible bundles during neuritogenesis in culture and in mature axons in situ

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