Post-translational modifications of intermediate filament proteins: mechanisms and functions

Abstract

Preface Intermediate filaments (IFs) are cytoskeletal and nucleoskeletal structures that provide mechanical and stress-coping resilience to cells, contribute to subcellular and tissue-specific biological functions, and facilitate intracellular communication. IF proteins, including nuclear lamins and cytoplasmic keratins, vimentin, desmin, neurofilaments, and glial fibrillary acidic protein, undergo various functionally important post-translational modifications (PTMs). Proteomic advances highlight the enormous complexity of IF PTMs, which include phosphorylation, glycosylation, sumoylation, acetylation, and prenylation, as well as their ability to regulate IF proteins, and are likely to reveal novel modifications. We would like to keep the original statement, since the revised version seems to imply that proteomic advances provide insight into the ability of PTMs to regulate IF proteins, which is not the case. Future studies will need to characterize their on–off mechanisms, cross-talk, and utility as biomarkers and targets for diseases involving the IF cytoskeleton.

Desmosomes and Intermediate Filaments: Their Consequences for Tissue Mechanics

“…Keratins show extensive sequence diversity, a feature that discriminates them from actins and tubulins (Schweizer et al 2006;Fletcher and Mullins 2010). This sequence diversity is responsible for their relative affinities to each other and to associated proteins, and enables isotype-specific posttranslational modifications (Hatzfeld and Franke 1985;Hofmann and Franke 1997;Snider and Omary 2014). In humans and the mouse, 28 type I keratins (KtyI) and 26 type II keratins (KtyII) genes are predominantly expressed as pair-specific combinations of types I and II keratin proteins, respectively, in epithelial cells and tissues.…”

“…Exposure of keratinocytes to stretch results in rapid and transient induction of MAPK ERK1/2 and SAP kinases (Kippenberger et al 2000;Yano et al 2004), accompanied by altered keratin expression, increased keratin phosphorylation and reorganization of keratin networks (Yano et al 2004;Snider and Omary 2014). At least in keratinocytes, mechanical stretching acts via induction of calcium influx, EGFR phosphorylation, and ERK1/2 activation (Yano et al 2004).…”

Sphingolipids inhibit vimentin-dependent cell migration

“…Phosphorylation serves to stimulate depolymerisation and turnover of the network. Conversely, dephosphorylation can stimulate network assembly and inhibit turnover (Snider and Omary, 2014). Recent work has shown that vimentin filaments are inhibitory for lamellipodia formation and ruffling, but are necessary for cell movement.…”

Keratin impact on PKCδ- and ASMase-mediated regulation of hepatocyte lipid raft size – implication for FasR-associated apoptosis

“…Notably, much of the IF protein diversity is determined by the N-and C-terminal domains (Coulombe and Omary, 2002), which are largely responsible for the spatiotemporal IF organization and their interactions with associated proteins, such as plectin (Coulombe and Wong, 2004;Green et al, 2005). In addition, these domains contain sites that can undergo posttranslational modifications in response to various stimuli, primarily phosphorylation sites that provide targets for several kinases, including mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) isoforms (Snider and Omary, 2014). Keratin modulation of such signaling cascades, namely those implicating PKCδ, can occur through participation of a cytoskeletal linker (e.g.…”