Intracellular Motility of Intermediate Filaments

Leube, Rudolf E.; Moch, Marcin; Windoffer, Reinhard

doi:10.1101/cshperspect.a021980

Cited by 22 publications

(14 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this way, we found distinct patterns of keratin dynamics in spontaneously migrating nHEKs. The overall spatial distribution resembled an adaptation of the flow distribution reported for circular shaped sessile cells 14,[33][34][35] to the polarized D-shape of migrating cells. Thus, retrograde flow was detected in the entire cell except for the back of the cell where anterograde flow occurred, which, however, is also inward directed.…”

Section: Discussionsupporting

confidence: 63%

Regulation of keratin network dynamics by the mechanical properties of the environment in migrating cells

Pora

Yoon

Dreissen

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

Keratin intermediate filaments provide mechanical resilience for epithelia. They are nevertheless highly dynamic and turn over continuously, even in sessile keratinocytes. the aim of this study was to characterize and understand how the dynamic behavior of the keratin cytoskeleton is integrated in migrating cells. By imaging human primary keratinocytes producing fluorescent reporters and by using standardized image analysis we detect inward-directed keratin flow with highest rates in the cell periphery. The keratin flow correlates with speed and trajectory of migration. Changes in fibronectincoating density and substrate stiffness induces concordant changes in migration speed and keratin flow. When keratinocytes are pseudo-confined on stripes, migration speed and keratin flow are reduced affecting the latter disproportionately. The regulation of keratin flow is linked to the regulation of actin flow. Local speed and direction of keratin and actin flow are very similar in migrating keratinocytes with keratin flow lagging behind actin flow. Conversely, reduced actin flow in areas of high keratin density indicates an inhibitory function of keratins on actin dynamics. together, we propose that keratins enhance persistence of migration by directing actin dynamics and that the interplay of keratin and actin dynamics is modulated by matrix adhesions.Cell migration is a highly complex process with relevance for physiological and pathological situations such as embryogenesis, wound healing and metastasis 1 . It is induced by chemical and biophysical cues. The cytoskeleton is at the core of generating effective locomotion by enabling successive steps of protrusion at the cell front and by facilitating the contractile events at the cell rear in parallel with the regulation of cell-matrix adhesions 2 . The cytoskeleton is composed of three major components, namely actin filaments, microtubules and intermediate filaments. The role of actin filaments and microtubules in cell migration has been extensively studied. In contrast, the contribution of intermediate filaments and especially of epithelial keratin intermediate filaments is still poorly understood 3 .Keratin filaments are the main class of cytoplasmic intermediate filaments in epithelial cells. They belong to a large multigene family encoded by more than 50 genes. Every keratin filament contains equal amounts of type I (acidic) and type II (basic) monomers. Obligatory heterodimers assemble in an antiparallel manner into non-polar tetramers, which further associate laterally and longitudinally to eventually generate 8-12 nm filaments 4-6 .The effect of keratin expression on migration depends on the keratin isoform, the cell type and the environment 3,7,8 . For example, the knockdown of K8/K18 reduces the invasion capacity of squamous cancer cells 9 but increases collective cell migration of cancer cells 10 . Depletion of the entire type II keratin gene cluster in mouse keratinocytes prevents keratin filament assembly and induces an increase in migration speed and invasiv...

show abstract

Section: Discussionsupporting

confidence: 63%

Regulation of keratin network dynamics by the mechanical properties of the environment in migrating cells

Pora

Yoon

Dreissen

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Network remodeling dynamics results from the coupling between assembly, disassembly and intracellular transport processes regulated by post-translational modifications of intermediate filament proteins as well as severing and annealing of filaments. Intracellular transport of IFs has been identified as a key process for the network dynamics; see, e.g., [2,3,4,5,6]. IFs regulated interactions with motors and structural linkers result in different modes of motility for assembled IF proteins in cells: slow, fast, bidirectional, retrograde, anterograde, and/or switching motions [7].…”

Section: Introductionmentioning

confidence: 99%

Stochastic modeling reveals how motor protein and filament properties affect intermediate filament transport

Dallon

Leduc

Etienne-Manneville

et al. 2019

Journal of Theoretical Biology

View full text Add to dashboard Cite

Intermediate filaments are a key component of the cytoskeleton. Their transport along microtubules plays an essential role in the control of the shape and structural organization of cells. To identify the key parameters responsible for the control of intermediate filament transport, we generated a model of elastic filament transport by microtubule-associated dynein and kinesin. The model is also applicable to the transport of any elastically-coupled cargoes. We investigate the effect of filament properties such as number of motor binding sites, length, and elasticity on motion of filaments. Additionally, we consider the effect of motor properties, i.e. off rates, on filament transport. When one motor has a catch bond off rate it dictates the motion, whereas when motors have the same type of off rate filaments can alternate between retrograde and anterograde motions. The elasticity of filaments optimizes the filament transport and the coordination of motors along the length of the filament.

show abstract

“…IFs are the strongest cytoskeletal elements ( Janmey et al, 1991 ), maintain their structure even as they replace subunits ( Colakoğlu and Brown, 2009 ), and protect cells from mechanical stress ( Leube et al, 2017 ). We, therefore, hypothesized that plakin-mediated recruitment of keratins into microridges stabilizes them, and that stabilization permits their elongation.…”

Section: Resultsmentioning

confidence: 99%

Keratins and plakin family cytolinker proteins control the length of epithelial microridge protrusions

Inaba

Chauhan

Loon

et al. 2020

eLife

View full text Add to dashboard Cite

Actin filaments and microtubules create diverse cellular protrusions, but intermediate filaments, the strongest and most stable cytoskeletal elements, are not known to directly participate in the formation of protrusions. Here we show that keratin intermediate filaments directly regulate the morphogenesis of microridges, elongated protrusions arranged in elaborate maze-like patterns on the surface of mucosal epithelial cells. We found that microridges on zebrafish skin cells contained both actin and keratin filaments. Keratin filaments stabilized microridges, and overexpressing keratins lengthened them. Envoplakin and Periplakin, Plakin family cytolinkers that bind F-actin and keratins, localized to microridges and were required for their morphogenesis. Strikingly, Plakin protein levels directly dictated microridge length. An actin-binding domain of Periplakin was required to initiate microridge morphogenesis, whereas Periplakin-keratin binding was required to elongate microridges. These findings separate microridge morphogenesis into distinct steps, expand our understanding of intermediate filament functions, and identify microridges as protrusions that integrate actin and intermediate filaments.

show abstract

Intracellular Motility of Intermediate Filaments

Cited by 22 publications

References 76 publications

Regulation of keratin network dynamics by the mechanical properties of the environment in migrating cells

Regulation of keratin network dynamics by the mechanical properties of the environment in migrating cells

Stochastic modeling reveals how motor protein and filament properties affect intermediate filament transport

Keratins and plakin family cytolinker proteins control the length of epithelial microridge protrusions

Contact Info

Product

Resources

About