Each node is clickable and results in a list of all proteins that are found in the connected organelles. Transcriptome analysis and classification of genes into tissue distribution categories Figure 6 shows that a larger portion of genes encoding proteins that localize to intermediate filaments are detected in some tissues or in many tissues, while a smaller portion are detected in all tissues, compared to all genes presented in the Cell Atlas.
This is well in-line with the known tissue type-dependent expression patterns of intermediate filament proteins Herrmann H et al. Figure 6. Bar plot showing the percentage of genes in different tissue distribution categories for intermediate filament-associated protein-coding genes compared to all genes in the Cell Atlas. Parikh K et al. Cell Res. Nat Methods. J Proteomics. J Proteome Res. PLoS One.
E Semple JW et al. We use cookies to enhance the usability of our website. If you continue, we'll assume that you are happy to receive all cookies. More information. Don't show this again. Search Fields » Search result. Gene name. Class Biological process Molecular function Disease. External id. Reliability Enhanced Supported Approved Uncertain. Reliability Supported Approved. Validation Supported Approved Uncertain. Annotation Intracellular and membrane Secreted - unknown location Secreted in brain Secreted in female reproductive system Secreted in male reproductive system Secreted in other tissues Secreted to blood Secreted to digestive system Secreted to extracellular matrix.
Searches Enhanced Supported Approved Uncertain Intensity variation Spatial variation Cell cycle intensity correlation Cell cycle spatial correlation Cell cycle biologically Custom data cell cycle dependant Cell cycle dependent protein Cell cycle independent protein Cell cycle dependent transcript Cell cycle independent transcript Multilocalizing Localizing 1 Localizing 2 Localizing 3 Localizing 4 Localizing 5 Localizing 6 Main location Additional location.
Type Protein Rna. Phase G1 S G2 M. Cell type. Expression Not detected Low Medium High. It is well-known that intermediate filament architecture is reorganized in response to cell migration stimuli.
Many studies have emphasized the contributions of polymerized intermediate filaments, but a novel role of soluble vimentin precursors has been proposed that is not necessarily related to biogenesis of intermediate filament network. Polymerized intermediate filaments can function as scaffolds while even intermediate filament precursors can play a role of adaptors to transport signaling molecules.
In particular, their head and tail domain have been proposed to buffer excess kinase activity. Such hyperphosphorylation of intermediate filaments can be detrimental or advantageous for the cell depending on the biological context Lai et al. Phosphorylated cytoplasmic intermediate filaments can also act as sequestering reservoirs to accommodate stress response or physiological processes.
Both phospho-vimentin and keratin provide binding affinity to sequester proteins like and therefore limit their availability to other target proteins in order to regulate processes like mitosis and signal transduction Tzivion et al. Cell proliferation and size are closely coupled to the binding of adaptor proteins and kinases to cytoplasmic intermediate filaments serving as either molecular scaffolds or sequestration sinks.
Perhaps the best example of phosphorylated intermediate filaments operating as docking sites for proteins is provided by members of the protein family. Keratins and vimentin orchestrate the local interaction of proteins with their multiple binding partners. K18 and interaction is closely coupled to the association of proteins with a host of phosphorylated signaling molecules that are involved in mitotic progression, such as Raf1 kinase and Akt Deng et al.
Similarly, phosphorylated vimentin also provides a binding sink for adaptor proteins Tzivion et al. Thus, phosphorylation of intermediate filaments has broad impacts to both intermediate filament polymerization status as well as modulation of cell signaling pathways.
Cellular mechanotransduction is an integration of multiple mechanical cues derived from sensing, transmission of force, and transduction into a biochemical response. There is extensive evidence that cell-cell, cell-ECM, and flow forces are actively sensed in different cellular contexts by the junctional protein complexes Riveline et al.
Different mechanical forces alter the structure, assembly, adhesive strength, function, and signaling of these adhesive complexes, which in turn has consequences to the cytoskeleton. Cytoplasmic intermediate filaments behave as an elastic and conductive network to transmit force and propagate mechanical stimuli within and between cells via adhesion complexes. As we detailed above, cytoplasmic intermediate filaments emerge as modulators of specific signal transduction pathways in a variety of biological contexts.
Abundant availability, overall cytoplasmic presence and subcellular reorganization dependent on cellular context, allows the cytoplasmic intermediate filaments to partake in various signaling pathways in a multitude of ways. Such a view presents cytoplasmic intermediate filaments to be apt to transduce mechanical stimuli during development while integrating an ever changing physical environment with cell signaling Figure 1.
Fluid flow shear stress plays important roles in the developing vasculature system. Perhaps more surprisingly fluid flow shear stress is also an important mechanical stimulus in tissues not often intuitively associated with exposure to fluid flow shear stresses, such as bone and glandular epithelia.
Fluid flow shear stress studies have shed some light on the role of intermediate filaments in mechanotransduction pathways. Cytoplasmic intermediate filaments alter their network organization most likely by mechanisms such as conformational change, changes in assembly, PTMs and others.
Mechanical forces such as shear stress can induce rapid reorganization of vimentin and keratin intermediate filament networks in various cell types, suggesting a role in spatial redistribution of intracellular force Helmke et al. Shear stress increases the keratin intermediate filament network stiffness in the peripheral region of the cytoplasm Sivaramakrishnan et al.
Phosphorylation of keratins in the regulatory head domain K18 pSer33 recruits binding of , which allow for dynamic exchange and remodeling of the network Sivaramakrishnan et al. In order to control against hyperphosphorylation induced disruption, keratin intermediate filaments recruit epiplakin, which perhaps serves as a chaperone during filament reorganization Spazierer et al.
Similarly, in response to shear stress, endothelial cells trigger a transition from cell-cell adhesion loading on VE-cadherin to interaction of PECAM Platelet endothelial cell adhesion molecule-1 with vimentin to stabilize cell-cell junctions Conway et al. In this manner, mechanical loads may be transferred from one cytoskeletal network to another.
Indeed keratin intermediate filaments exhibit less motion when actin-myosin II rigidity is increased, likely a consequence of stress generated by actomyosin being transmitted to pre-stress the keratin intermediate filament network Nolting and Koster, Decoupling the intermediate filaments from the mechanotransduction pathway has revealed hitherto unrecognized roles of intermediate filaments in this process. For instance, cells with inhibited vimentin expression display reduced mechanical resistance to the effects of flow Tsuruta and Jones, Likewise mutant keratin intermediate filament network is unable to withstand mechanical stress Ma et al.
Moreover, exploiting stress conditions in the absence of plectin, triggers prominent fragmentation of the intermediate filament network Gregor et al. In agreement with these findings, cytoplasmic intermediate filaments perceive tension relayed by the upstream mechanosensors and, in response, initiate rearrangements to function as stress buffers. How cytoplasmic intermediate filaments sense tension remains poorly understood.
A speculative possibility is that cytoplasmic intermediate filaments alter their conformation or assembly upon stress to reveal cryptic sites crucial for sensing tension. For example, vimentin Cys site gets blocked under tension Johnson et al. Cytoplasmic intermediate filaments of all types exhibit plasticity in their structural folding which may offer both elasticity and potential for cryptic unmasking. These conformational changes in intermediate filament structure within the polymerized filament could have profound impacts to cell signaling as detailed earlier, and offers a bridge between managing the physical architecture and biochemical signaling.
Like their actin and microtubule counterparts, intermediate filaments have profound influence over cellular functions, with migration being amongst the most dynamic. A traditional view of intermediate filaments, particularly keratins, is that their association with stable adhesions provides for a general inhibition of migratory potential. And indeed, depletion or mutation of keratin alters, often increasing, migration rates of cancer cells which is likely to contribute to metastasis Busch et al.
Additionally, impaired directional migration has been observed in MCF-7, HeLa, and Panc-1 epithelial cells lacking keratin expression Long et al. In contrast, upregulation of vimentin is seen during wound healing Eckes et al. In addition to being an often used general marker of epithelial-mesenchymal transition EMT , vimentin has a direct role in the migratory phenotype of cells having undergone EMT Vuoriluoto et al.
Furthermore, treatment of cells with diverse bioactive molecules such as withaferin A Grin et al. The aforementioned view of keratins as inhibiting migration and vimentin as promoting migration, while convenient, greatly oversimplifies the actual role that intermediate filaments play in migration. In fact, some keratins, such as K14, can promote cell migration, and their expression is correlated with both invasive carcinomas and migration during embryonic development Sun et al.
Still other keratins, like K19, seem to have multiple functionalities that may greatly depend on the expression levels and more nuanced roles in modification of signal transduction pathways Ohtsuka et al. How then might intermediate filaments impact migration when they are doing more than simply resisting motility? Different modes of migration, whether random or directed, individual or collective, require the cytoskeleton to generate the structures that drive cell movement.
Unique cytoskeletal structures determine and differentiate the protrusive cell front and a retracting rear. Akin to the differences that one sees in actin organization in the front vs. Intermediate filaments extend through the rear and the perinuclear region of the cell, whereas vimentin particles are predominantly present in the lamellipodia Helfand et al.
Consistent with this correlational observation, it has been shown that increased presence of vimentin particles precedes lamellipodia formation Helfand et al.
Induced disruption of vimentin intermediate filament networks by microinjection of vimentin mimetic peptide 1A or 2B2 induces membrane ruffling at cell edges previously devoid of lamellipodia Goldman et al. Furthermore, non-filamentous vimentin or ULF's were shown to be in close proximity with smaller FAs while stable vimentin filaments were in vicinity of large FAs Terriac et al.
This suggests that assembly states of vimentin seems not only affect lamellipodia formation but may also be involved in establishing the anisotropy of focal contacts and focal adhesions to modulate efficient migration.
Notably, roles for intermediate filaments in migration are not limited to vimentin. In isolated keratinocytes, keratin particles primarily reside in the lamellipodia and keratin intermediate filaments extend through the cell body to the trailing edge Kolega, ; Kolsch et al. Furthermore, these cells also exhibit asymmetric keratin dynamics, keratin particles prominently forming in the lamellipodia, further grow by elongation and fusion until integration into the peripheral network Kolsch et al.
In some non-epithelial cells that express keratins such as mesodermal cells, the correlation between cell protrusive polarity and reorganization of keratin intermediate filament network remains Weber et al.
In single multipolar mesodermal cells, lacking a definite protrusive polarity, keratin intermediate filaments span across the cell cytoplasm and yet are notably absent from protrusions Weber et al.
It remains to be determined whether the location of the keratin filaments per-se is a determinant of protrusive activity. However, in support of this hypothesis computational models predict that lamellipodia formation occurs in the direction opposite to keratin network formation Kim et al.
Keratins mediate stabilization of hemidesmosomes in some cells, and through promotion of these stable contacts, migration is inhibited Seltmann et al. The influence of intermediate filaments on migration may have as much to do with the types of adhesions with which they are associated focal contacts vs.
How do intermediate filaments guide migration when cells are moving cohesively? Front-rear polarization depends on mechanical cues exerted at cell-cell junctions. Formation of adherens junctions, but not desmosomes, generates tensile stress in tissues Harris et al. Perturbing such intercellular contacts either by function blocking antibodies, chelation of calcium or protein knockdown, attenuates stresses mediated by classical cadherins and collective cell migration Ganz et al.
Application of local tension on single mesodermal cells induces reorganization of the intermediate filaments at cell-cell adhesion sites via plakoglobin Weber et al.
Similarly, ex-vivo embryonic Xenopus tissue explants arrange keratin intermediate filaments in a manner similar to single cells under tension Weber et al. Reorganization of keratin cytoskeleton is also observed during epithelial sheet migration Long et al. Intercellular tissue tension also contributes to integrin mediated traction forces Dzamba et al.
Thus, both cell-cell and cell-ECM interactions establish physicomechanical guidance cues. Extending lamellipodia of repair cells of wound healing are frequently enriched with vimentin particles Menko et al. Likewise keratin particles are observed in the leading edge lamellipodia of epithelial cells Kolsch et al.
Thus, intermediate filaments break the symmetry and are arranged in an asymmetrical array to support polarized migration. We argue that this asymmetry may facilitate establishment of differential front and rear microenvironments necessary for efficient migration.
The small GTPase Rac1 is a probable mechanism for the differential localization of cytoplasmic intermediate filaments, and has direct implications to regulation of migration and polarity. Optimum levels of Rac1 play a critical role in protrusion formation to ensure directional cell migration Pankov et al. Spatial and temporal activation of Rac1 is sufficient to promote collective cell migration in different models Theveneau et al. In single migratory fibroblasts, local induction of Rac1, promotes disassembly of vimentin intermediate filaments, locally inducing membrane ruffles, while the assembled filaments are maintained in the rear Helfand et al.
These data suggest that cell-cell contacts may serve a mechanosensing and signaling function by stably recruiting intermediate filaments where they locally suppress Rac activity, and cell protrusions, at the posterior of collectively migrating cells Figure 2. Figure 2. Intermediate filaments and the establishment of cellular subdomains to drive directional migration.
A Intermediate filaments exist in cells as monomer, filament precursors, and mature filaments. While mature intermediate filaments connect to cell adhesions, the nuclear lamina and span across the cell body, they are often notably absent from protrusions.
Filament precursors are abundant in protrusions where Rac is active. B Tension red arrows on cell-cell adhesions recruits intermediate filaments. Persistent localization of intermediate filaments proximal to cell-cell adhesions may establish distinct non-protrusive Rac-inhibited zones. Areas of the cell with lesser tension on cell-cell contacts do not recruit intermediate filaments, creating Rac-permissive zones that promote protrusions that lead to directional migration blue arrow.
Despite this subcellular localization, intermediate filaments remain dynamic through non-polar subunit exchange dashed arrow. C Stable cell-cell adhesions and the differential intercellular tension present across tissues may promote persistent collective cell migration behavior blue arrow.
Intermediate filaments simultaneously maintain tissue integrity while influencing cell signaling pathways that determine cell polarity and protrusive behavior. The antagonistic relationship between cytoplasmic intermediate filaments and Rac1 may act as a mechanochemical switch that determines which of two mutually exclusive signaling states will occur.
A similar switch exists between merlin and Rac1. A negative feedback loop between merlin-Rac1 controls the protrusion promoting state in the front end of the cell and protrusion inhibiting state at the rear end of the cells Das et al.
Stable cell-cell adhesions promote persistent directionality through this negative feedback loop Das et al. Interestingly both intermediate filaments and Merlin are associated with stable cadherin-mediated cell-cell contacts. Perhaps future studies will find a molecular mechanistic link given their common function in regulating polarity of collectively migrating cells. Elucidating the role of many cytoplasmic intermediate filaments in embryonic development has proven to be challenging due to functional redundancy and complexity within the family.
Targeted deletion of K18 failed to block embryonic development in mice because of the presence of K19, demonstrating the functional redundancy within the protein family Magin et al. Despite this dominant role in the extraembryonic tissue, various keratin knockouts have surprisingly mild developmental phenotypes considering the known roles intermediate filaments play in adhesion.
Defects in specific tissues at later stages where keratins are expressed argues a role for keratins in late tissue morphogenesis, homeostasis and physiological function Bouameur and Magin, , but a role for keratins in early embryogenesis has largely remained elusive in mouse models. As with many of the keratin knockout mice, mice lacking vimentin surprisingly undergo embryonic development quite normally, however, exhibit impaired wound healing Eckes et al.
The epidermal skin is broadly comprised of proliferative basal, stratified suprabasal, and terminally differentiated cornified layers. Each of these layers expresses a unique combinations of Type I and II keratins. Additional keratins, such as K6, K7, K9, K17, K76, have limited expression in the specialized epidermal regions like the palms and hair follicles.
What is more, perturbation of keratin expression in these layers also results in the disruption of the homeostasis of the epidermis as it matures into distinct layers. Although functional redundancy may obscure the role of specific keratins Reichelt et al. Keratins also coordinate cell growth and protein biosynthesis by accurate localization of GLUT-1 and -3 and consequentially optimize regulation of mTOR pathway as evidenced by keratin Type II knockout mice Vijayaraj et al.
Collectively, these data point toward an important role for cytoplasmic intermediate filaments in modulating cell growth and proliferation through their impact on cell signaling pathways. Cells migrate collectively in a coordinated manner to accomplish various tasks for development of the organism, from gametogenesis to morphogenesis to organogenesis. Collective cell migration allows whole groups of cells to move toward their final destination most efficiently while maintaining tissue cohesivity and tissue-specific characteristics.
All the while, these cells can transmit signals to each other and effectively navigate the complex and changing environment within the developing embryo. Disruption of the keratin network in the amphibian embryo tells quite a different story than mice about the importance of intermediate filaments in early embryogenesis.
Disruption of keratin by either targeting protein expression Heasman et al. Pointing to a role in collective migration events, polarized protrusive cell behavior of the mesoderm is lost in the absence of K8 expression in Xenopus embryos Weber et al.
Collective cell movements are also perturbed in keratin mutant mice, albeit at stages of organogenesis and tissue maintenance.
Vimentin plays a role in promoting stemness of mammary epithelial cells which provide the basis for mammary gland growth. Ductal outgrowth is significantly delayed in mammary glands from vimentin knockout mice and the lumen is slightly enlarged Virtakoivu et al. Both populations of mammary cells are involved in the branching morphogenesis of the tissue. Interestingly during the initial development of the mammary placode in the embryonic mouse, these invasive migratory cells express both K8 and K14 Sun et al.
Only recently have selective promoters for basal mammary epithelial cells become available. Morphogenesis of epidermal and muscle tissue in Caenorhabditis elegans provides a particular elegant example of the interplay between intermediate filaments and mechanotransduction pathways during development.
With PIX-1 at the hemidesmosome, Rac is activated, which further stimulates PAK-1 activity and subsequent phosphorylation of intermediate filaments Zhang et al.
Phosphorylation of intermediate filaments through this mechanism drives remodeling and maturation of the hemidesmosome and the associated intermediate filament network Zhang et al. Hemidesmosomes behave as mechanosensors that further relay the tension by activation of specific signaling pathway that promotes epithelial morphogenesis Zhang et al.
Indeed, coordination between the epidermis and muscle cells is absolutely essential to epidermal morphogenesis that elongates the worm, and cytoplasmic intermediate filaments are vital to this process Woo et al. Migration driven by cell-cell adhesions has roles very early in development, even as early as development of gametes.
Tension sensing through E-cadherin plays a critical role in controlling directionality of migration of border cells in the Drosophila ovary Cai et al. As with many collectively migrating cells, asymmetric Rac activity also plays a key role in the steering of these migrating collectives Wang et al.
For some time, cytoplasmic intermediate filaments were believed to be absent from many non-chordates including arthropods. Knockdown of this Tm1 isoform impairs border cell migration, unlike knockdown of other Tm1 isoforms.
Intermediate filaments are the next frontier for understanding how cells cope with mechanical stimuli and integrate these signals with cellular function. Current data bolsters the notion that cytoplasmic intermediate filaments provide a unique scaffolding framework that regulates major mechanotransduction events initiated through cellular adhesions.
Moreover, intermediate filaments function in these mechanotransduction processes in a non-redundant manner that cannot be compensated by other cytoskeletal networks during development. New innovative methods will have to be devised to tackle the details of how intermediate filaments are regulated in terms of turnover, dynamic exchange, and other remodeling events in vivo.
Although, various signaling pathway relationships to intermediate filaments have been found, the molecular mechanism by which intermediate filaments effect signaling is not always clear. For a few proteins, direct interaction with intermediate filaments are known to exist. Subcellular compartmentalization of the different intermediate filament polymerization states i. Intermediate filament filaments and particles may form a differential composite network that, in coordination with the other cytoskeletal elements, endures and responds to changing physical parameters that cells experience during development.
Significant headway has been made to investigate the relationship between intermediate filaments and the actin and microtubule networks. Still, questions remain particularly related to the in vivo functionality of intermediate filament elasticity.
In this regard, intermediate filaments could store substantial potential energy and enable cell contractility through a non-actomyosin mechanism. Both actomyosin and intermediate filaments could work cooperatively as dynamic elastic components. Likewise, nuanced differences between various keratin proteins and vimentin in regulation, turnover rates, and mechanical properties are likely optimized for different cell and tissue-specific functions.
Intermediate filaments as elastic, but resilient, cytoskeletal structures may undergo conformational changes due to mechanical stresses that unmask cryptic binding sites within the polymerized filament.
If great enough, these stresses might otherwise rupture a cell or another cytoskeletal component, but intermediate filaments are uniquely suited to cope with these greater forces. For cytoplasmic intermediate filaments, they become a strain sensor- in essence, only permitting certain cell signaling events to occur when strain is applied. Developmental morphogenesis and cell migration are but two processes for which these signals would be important, yet important ones since dramatic tissue shaping occurs on a rapid timescale.
As much as intermediate filaments have historically been touted as the keepers of cellular mechanical integrity, investigating them as dynamic components of cellular mechanosensor complexes is demanded.
If we think about different types of adhesions as an interdependent network, then perhaps we can confer a similar thought process to how we think about cytoskeletal networks.
Given the coordination in localization, function, and integration with signal transduction pathways, our longstanding conceptual models of discrete adhesive structures with separate cytoskeletal networks may be long overdue for a re-thinking. As much as we have learned about the role of cell adhesions and actomyosin in force-induced signal transduction in the last decade, the potential exists for an equally robust phase of discovery about intermediate filaments and their role in mechanotransduction during development.
RS and GW shared equally in the conceptual development, literature research, and writing of the manuscript. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
We would like to thank the members of the Weber laboratory, especially Shalaka Paranjpe, Richard Mariani, and Huri Mucahit, for helpful discussions leading to the production of this manuscript. Ackbarow, T. Alpha-helical protein networks are self-protective and flaw-tolerant. Almeida, F. The cytolinker plectin regulates nuclear mechanotransduction in keratinocytes. Cell Sci. Skin fragility and impaired desmosomal adhesion in mice lacking all keratins.
Control of cell-cell forces and collective cell dynamics by the intercellular adhesome. Cell Biol. Bear, M. Alpha-catulin co-localizes with vimentin intermediate filaments and functions in pulmonary vascular endothelial cell migration via ROCK.
Beil, M. Sphingosylphosphorylcholine regulates keratin network architecture and visco-elastic properties of human cancer cells. Bhattacharya, R. Bjerke, M. FAK is required for tension-dependent organization of collective cell movements in Xenopus mesendoderm. Blikstad, I. Vimentin filaments are assembled from a soluble precursor in avian erythroid cells. Bordeleau, F. Cell 21, — Bouameur, J.
Lessons from animal models of cytoplasmic intermediate filament proteins. Interaction of plectin with keratins 5 and dependence on several plectin domains and keratin quaternary structure. Burgstaller, G.
Keeping the vimentin network under control: cell-matrix adhesion-associated plectin 1f affects cell shape and polarity of fibroblasts. Busch, T. Keratin 8 phosphorylation regulates keratin reorganization and migration of epithelial tumor cells. Cai, D. Mechanical feedback through E-cadherin promotes direction sensing during collective cell migration. Cell , — Cary, R. Vimentin's tail interacts with actin-containing structures in vivo. PubMed Abstract Google Scholar.
Chang, I. Chang, L. The dynamic properties of intermediate filaments during organelle transport. Chernyatina, A. Atomic structure of the vimentin central alpha-helical domain and its implications for intermediate filament assembly. Cheung, K. Collective invasion in breast cancer requires a conserved basal epithelial program.
Polyclonal breast cancer metastases arise from collective dissemination of keratin expressing tumor cell clusters. Cho, A. An atypical tropomyosin in Drosophila with intermediate filament-like properties. Cell Rep. Chou, Y. The regulation of intermediate filament reorganization in mitosis. Coleman, T.
Continuous growth of vimentin filaments in mouse fibroblasts. Conway, D. Correia, I. Integrating the actin and vimentin cytoskeletons: adhesion-dependent formation of fimbrin-vimentin complexes in macrophages. Das, T. A molecular mechanotransduction pathway regulates collective migration of epithelial cells. Deng, M. Lactotransferrin acts as a tumor suppressor in nasopharyngeal carcinoma by repressing AKT through multiple mechanisms.
Oncogene 32, — Dmello, C. Vimentin-mediated regulation of cell motility through modulation of beta4 integrin protein levels in oral tumor derived cells. Dodemont, H. Structure of an invertebrate gene encoding cytoplasmic intermediate filament IF proteins : implications for the origin and the diversification of IF proteins. EMBO J. Dupin, I. Cytoplasmic intermediate filaments mediate actin-driven positioning of the nucleus.
Dzamba, B. Cadherin adhesion, tissue tension, and noncanonical Wnt signaling regulate fibronectin matrix organization. Cell 16, — Eckert, B. Alteration of intermediate filament distribution in PtK1 cells by acrylamide. Eckes, B. Impaired wound healing in embryonic and adult mice lacking vimentin. Impaired mechanical stability, migration and contractile capacity in vimentin-deficient fibroblasts.
Esue, O. A direct interaction between actin and vimentin filaments mediated by the tail domain of vimentin. Ewald, A. Collective epithelial migration and cell rearrangements drive mammary branching morphogenesis. Cell 14, — Flitney, E. Insights into the mechanical properties of epithelial cells: the effects of shear stress on the assembly and remodeling of keratin intermediate filaments.
Fogl, C. Mechanism of intermediate filament recognition by plakin repeat domains revealed by envoplakin targeting of vimentin. Fois, G. Effects of keratin phosphorylation on the mechanical properties of keratin filaments in living cells. Fortier, A. Keratin 8 and 18 loss in epithelial cancer cells increases collective cell migration and cisplatin sensitivity through claudin1 up-regulation.
Franke, W. Different intermediate-sized filaments distinguished by immunofluorescence microscopy. Antibody to prekeratin. Decoration of tonofilament-like arrays in various cells of epithelial character.
Cell Res. Diversity of cytokeratins. Franz, J. Intermediate-size filaments in a germ cell: expression of cytokeratins in oocytes and eggs of the frog Xenopus. Fudge, D. The intermediate filament network in cultured human keratinocytes is remarkably extensible and resilient. Fujiwara, S. Interplay between Solo and keratin filaments is crucial for mechanical force-induced stress fiber reinforcement.
Cell 58, — Ganz, A. Eight rods are aligned in a staggered array with another eight rods, and these components all twist together to form the rope-like conformation of an intermediate filament.
Cytoskeletal filaments provide the basis for cell movement. For instance, cilia and eukaryotic flagella move as a result of microtubules sliding along each other. In fact, cross sections of these tail-like cellular extensions show organized arrays of microtubules.
Other cell movements, such as the pinching off of the cell membrane in the final step of cell division also known as cytokinesis are produced by the contractile capacity of actin filament networks. Actin filaments are extremely dynamic and can rapidly form and disassemble. In fact, this dynamic action underlies the crawling behavior of cells such as amoebae. At the leading edge of a moving cell, actin filaments are rapidly polymerizing; at its rear edge, they are quickly depolymerizing Figure 5.
A large number of other proteins participate in actin assembly and disassembly as well. Figure 5: Cell migration is dependent on different actin filament structures. These protrusive structures contain actin filaments, with elongating barbed ends orientated toward the plasma membrane. B During cellular arm extension, the plasma membrane sticks to the surface at the leading edge. C Next, the nucleus and the cell body are pushed forward through intracellular contraction forces mediated by stress fibers.
D Then, retraction fibers pull the rear of the cell forward. Filopodia: molecular architecture and cellular functions. Nature Reviews Molecular Cell Biology 9, All rights reserved. Figure Detail. This page appears in the following eBook. Aa Aa Aa. Microtubules and Filaments. What Is the Cytoskeleton Made Of?
The cytoskeleton of eukaryotic cells is made of filamentous proteins, and it provides mechanical support to the cell and its cytoplasmic constituents.
All cytoskeletons consist of three major classes of elements that differ in size and in protein composition. Microtubules are the largest type of filament, with a diameter of about 25 nanometers nm , and they are composed of a protein called tubulin. Actin filaments are the smallest type, with a diameter of only about 6 nm, and they are made of a protein called actin.
Intermediate filaments, as their name suggests, are mid-sized, with a diameter of about 10 nm. Unlike actin filaments and microtubules, intermediate filaments are constructed from a number of different subunit proteins. What Do Microtubules Do? Figure 1. What Do Actin Filaments Do? Figure 2. What Do Intermediate Filaments Do? Figure 4: The structure of intermediate filaments.
Intermediate filaments are composed of smaller strands in the shape of rods.
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