Providing cellular signposts – Post‐translational modifications of intermediate filaments

Hyder, Claire L.; Pallari, Hanna‐Mari; Kochin, Vitaly; Eriksson, John E.

doi:10.1016/j.febslet.2008.04.064

Cited by 78 publications

(72 citation statements)

References 106 publications

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“…Subsequent studies have demonstrated specific phosphorylation sites that are involved in regulating the dynamic exchange of subunits (reviewed in refs. 71,72). The phosphate turnover maintaining this dynamic exchange is driven by a high protein phosphatase activity on IFs, something that is also necessary for maintaining the structural integrity of IF polymers (73,74).…”

Section: A Turning Point In If Research: Ifs Are Dynamic Cytoarchitecmentioning

confidence: 99%

“…These and other novel functions of IFs are further highlighted here: the examples below are not intended to be comprehensive, but rather present illustrative models of how IFs may function in regulating cellular functions and signal processing (for details on the signaling-related functions of IFs, see refs. 71,[99][100][101][102].…”

Section: The Switch In the If Paradigm: From Structural Proteins To Mmentioning

confidence: 99%

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Introducing intermediate filaments: from discovery to disease

Eriksson

Dechat²,

Grin³

et al. 2009

J. Clin. Invest.

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380

366

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It took more than 100 years before it was established that the proteins that form intermediate filaments (IFs) comprise a unified protein family, the members of which are ubiquitous in virtually all differentiated cells and present both in the cytoplasm and in the nucleus. However, during the past 2 decades, knowledge regarding the functions of these structures has been expanding rapidly. Many disease-related roles of IFs have been revealed. In some cases, the molecular mechanisms underlying these diseases reflect disturbances in the functions traditionally assigned to IFs, i.e., maintenance of structural and mechanical integrity of cells and tissues. However, many disease conditions seem to link to the nonmechanical functions of IFs, many of which have been defined only in the past few years.

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Section: A Turning Point In If Research: Ifs Are Dynamic Cytoarchitecmentioning

confidence: 99%

Section: The Switch In the If Paradigm: From Structural Proteins To Mmentioning

confidence: 99%

Introducing intermediate filaments: from discovery to disease

Eriksson

Dechat²,

Grin³

et al. 2009

J. Clin. Invest.

Self Cite

380

366

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“…1A-C), and it is well known that vimentin regulates cell motility (Chung et al, 2013), we hypothesized that these lipids might regulate vimentin. Phosphorylation is one of the primary posttranslational modifications (PTM) regulating vimentin organisation (Hyder et al, 2008;Izawa and Inagaki, 2006). Vimentin has more than 20 phosphorylation sites of which at least 11 are physiologically relevant in vivo (Eriksson et al, 2004).…”

Section: Sphingolipids Induce Phosphorylation Of Vimentin On S71mentioning

confidence: 99%

“…Vimentin expression is associated with metastatic ability and it is widely accepted to be important for migratory functions (Chung et al, 2013;Nieminen et al, 2006). One key way that vimentin regulates cell motility is through dynamic reorganisation of its constituent filament network, which is regulated by phosphorylation on the N-terminus (Hyder et al, 2008;Ivaska et al, 2007). Phosphorylation serves to stimulate depolymerisation and turnover of the network.…”

Section: Introductionmentioning

confidence: 99%

Sphingolipids inhibit vimentin-dependent cell migration

Hyder

Kemppainen

Isoniemi

et al. 2015

Journal of Cell Science

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The sphingolipids, sphingosine 1-phosphate (S1P) and sphingosylphosphorylcholine (SPC), can induce or inhibit cellular migration. The intermediate filament protein vimentin is an inducer of migration and a marker for epithelial-mesenchymal transition. Given that keratin intermediate filaments are regulated by SPC, with consequences for cell motility, we wanted to determine whether vimentin is also regulated by sphingolipid signalling and whether it is a determinant for sphingolipid-mediated functions. In cancer cells where S1P and SPC inhibited migration, we observed that S1P and SPC induced phosphorylation of vimentin on S71, leading to a corresponding reorganization of vimentin filaments. These effects were sphingolipid-signalling-dependent, because inhibition of either the S1P 2 receptor (also known as S1PR2) or its downstream effector Rho-associated kinase (ROCK, for which there are two isoforms ROCK1 and ROCK2) nullified the sphingolipid-induced effects on vimentin organization and S71 phosphorylation. Furthermore, the anti-migratory effect of S1P and SPC could be prevented by expressing S71-phosphorylation-deficient vimentin. In addition, we demonstrated, by using wild-type and vimentin-knockout mouse embryonic fibroblasts, that the sphingolipid-mediated inhibition of migration is dependent on vimentin. These results imply that this newly discovered sphingolipid-vimentin signalling axis exerts brake-and-throttle functions in the regulation of cell migration.

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“…By contrast, the head and tail domains exhibit large variations in sequence and size and are thought to modify the interaction of IF subunits through post-translational modifications. The flanking head and tail domains are the preferential regions that undergo these modifications (Omary et al, 1998;Omary et al, 2006;Hyder et al, 2008), albeit rod domain IF post-translational modifications (e.g. sumoylation) are emerging (Zhang and Sarge, 2008;Snider et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Unique amino acid signatures that are evolutionarily conserved distinguish simple-type, epidermal and hair keratins

Strnad

Usachov

Debès

et al. 2011

Journal of Cell Science

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SummaryKeratins (Ks) consist of central a-helical rod domains that are flanked by non-a-helical head and tail domains. The cellular abundance of keratins, coupled with their selective cell expression patterns, suggests that they diversified to fulfill tissue-specific functions although the primary structure differences between them have not been comprehensively compared. We analyzed keratin sequences from many species: K1, K2, K5, K9, K10, K14 were studied as representatives of epidermal keratins, and compared with K7, K8, K18, K19, K20 and K31, K35, K81, K85, K86, which represent simple-type (single-layered or glandular) epithelial and hair keratins, respectively. We show that keratin domains have striking differences in their amino acids. There are many cysteines in hair keratins but only a small number in epidermal keratins and rare or none in simple-type keratins. The heads and/or tails of epidermal keratins are glycine and phenylalanine rich but alanine poor, whereas parallel domains of hair keratins are abundant in prolines, and those of simple-type epithelial keratins are enriched in acidic and/or basic residues. The observed differences between simple-type, epidermal and hair keratins are highly conserved throughout evolution. Cysteines and histidines, which are infrequent keratin amino acids, are involved in de novo mutations that are markedly overrepresented in keratins. Hence, keratins have evolutionarily conserved and domain-selectively enriched amino acids including glycine and phenylalanine (epidermal), cysteine and proline (hair), and basic and acidic (simple-type epithelial), which reflect unique functions related to structural flexibility, rigidity and solubility, respectively. Our findings also support the importance of human keratin 'mutation hotspot' residues and their wild-type counterparts.

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Providing cellular signposts – Post‐translational modifications of intermediate filaments

Cited by 78 publications

References 106 publications

Introducing intermediate filaments: from discovery to disease

Introducing intermediate filaments: from discovery to disease

Sphingolipids inhibit vimentin-dependent cell migration

Unique amino acid signatures that are evolutionarily conserved distinguish simple-type, epidermal and hair keratins

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