scholarly journals Crawling from soft to stiff matrix polarizes the cytoskeleton and phosphoregulates myosin-II heavy chain

2012 ◽  
Vol 199 (4) ◽  
pp. 669-683 ◽  
Author(s):  
Matthew Raab ◽  
Joe Swift ◽  
P.C. Dave P. Dingal ◽  
Palak Shah ◽  
Jae-Won Shin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Myosin Ii ◽  
Stress Fibers ◽  
Site Specific ◽  
Soft Matrix ◽  
3D Collagen ◽  
The Difference ◽  
Rigid Surfaces ◽  
Tissue Matrix ◽  
In Cells

On rigid surfaces, the cytoskeleton of migrating cells is polarized, but tissue matrix is normally soft. We show that nonmuscle MIIB (myosin-IIB) is unpolarized in cells on soft matrix in 2D and also within soft 3D collagen, with rearward polarization of MIIB emerging only as cells migrate from soft to stiff matrix. Durotaxis is the tendency of cells to crawl from soft to stiff matrix, and durotaxis of primary mesenchymal stem cells (MSCs) proved more sensitive to MIIB than to the more abundant and persistently unpolarized nonmuscle MIIA (myosin-IIA). However, MIIA has a key upstream role: in cells on soft matrix, MIIA appeared diffuse and mobile, whereas on stiff matrix, MIIA was strongly assembled in oriented stress fibers that MIIB then polarized. The difference was caused in part by elevated phospho-S1943–MIIA in MSCs on soft matrix, with site-specific mutants revealing the importance of phosphomoderated assembly of MIIA. Polarization is thus shown to be a highly regulated compass for mechanosensitive migration.

scholarly journals Plectin sidearms mediate interaction of intermediate filaments with microtubules and other components of the cytoskeleton.

1996 ◽  
Vol 135 (4) ◽  
pp. 991-1007 ◽  
Author(s):  
T M Svitkina ◽  
A B Verkhovsky ◽  
G G Borisy
Keyword(s):  
Transgenic Mice ◽  
Mammalian Cell ◽  
Intermediate Filaments ◽  
Myosin Ii ◽  
Immunogold Labeling ◽  
Stress Fibers ◽  
Cross Links ◽  
Membrane Components ◽  
In Cells

By immunogold labeling, we demonstrate that "millipede-like" structures seen previously in mammalian cell cytoskeletons after removal of actin by treatment with gelsolin are composed of the cores of vimentin IFs with sidearms containing plectin. These plectin sidearms connect IFs to microtubules, the actin-based cytoskeleton and possibly membrane components. Plectin binding to microtubules was significantly increased in cells from transgenic mice lacking IFs and was reversed by microinjection of exogenous vimentin. These results suggest the existence of a pool of plectin which preferentially associates with IFs but may also be competed for by microtubules. The association of IFs with microtubules did not show a preference for Glu-tubulin. Nor did it depend upon the presence of MAP4 since plectin links were retained after specific immunodepletion of MAP4. The association of IFs with stress fibers survived actin depletion by gelsolin suggesting that myosin II minifilaments or components closely associated with them may play a role as plectin targets. Our results provide direct structural evidence for the hypothesis that plectin cross-links elements of the cytoskeleton thus leading to integration of the cytoplasm.

scholarly journals The tension mounts: Stress fibers as force-generating mechanotransducers

2013 ◽  
Vol 200 (1) ◽  
pp. 9-19 ◽  
Author(s):  
Keith Burridge ◽  
Erika S. Wittchen
Keyword(s):  
Tissue Culture ◽  
Physical Environment ◽  
Actin Filaments ◽  
Striated Muscle ◽  
Myosin Ii ◽  
Stress Fibers ◽  
New Work ◽  
Mechanical Tension ◽  
And Behavior ◽  
In Cells

Stress fibers (SFs) are often the most prominent cytoskeletal structures in cells growing in tissue culture. Composed of actin filaments, myosin II, and many other proteins, SFs are force-generating and tension-bearing structures that respond to the surrounding physical environment. New work is shedding light on the mechanosensitive properties of SFs, including that these structures can respond to mechanical tension by rapid reinforcement and that there are mechanisms to repair strain-induced damage. Although SFs are superficially similar in organization to the sarcomeres of striated muscle, there are intriguing differences in their organization and behavior, indicating that much still needs to be learned about these structures.

scholarly journals The underestimated role of the microphthalmia-associated transcription factor (MiTF) in normal and pathological haematopoiesis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alessia Oppezzo ◽  
Filippo Rosselli
Keyword(s):  
Stem Cells ◽  
Gene Networks ◽  
Bone Marrow Failure ◽  
Phenotypic Traits ◽  
Expression Of Genes ◽  
Specific Setting ◽  
Haematopoietic System ◽  
Abnormal Pigmentation ◽  
In Cells

AbstractHaematopoiesis, the process by which a restrained population of stem cells terminally differentiates into specific types of blood cells, depends on the tightly regulated temporospatial activity of several transcription factors (TFs). The deregulation of their activity or expression is a main cause of pathological haematopoiesis, leading to bone marrow failure (BMF), anaemia and leukaemia. TFs can be induced and/or activated by different stimuli, to which they respond by regulating the expression of genes and gene networks. Most TFs are highly pleiotropic; i.e., they are capable of influencing two or more apparently unrelated phenotypic traits, and the action of a single TF in a specific setting often depends on its interaction with other TFs and signalling pathway components. The microphthalmia-associated TF (MiTF) is a prototype TF in multiple situations. MiTF has been described extensively as a key regulator of melanocyte and melanoma development because it acts mainly as an oncogene. Mitf-mutated mice show a plethora of pleiotropic phenotypes, such as microphthalmia, deafness, abnormal pigmentation, retinal degeneration, reduced mast cell numbers and osteopetrosis, revealing a greater requirement for MiTF activity in cells and tissue. A growing amount of evidence has led to the delineation of key roles for MiTF in haematopoiesis and/or in cells of haematopoietic origin, including haematopoietic stem cells, mast cells, NK cells, basophiles, B cells and osteoclasts. This review summarizes several roles of MiTF in cells of the haematopoietic system and how MiTFs can impact BM development.

scholarly journals Specification of Actin Filament Function and Molecular Composition by Tropomyosin Isoforms

2003 ◽  
Vol 14 (3) ◽  
pp. 1002-1016 ◽  
Author(s):  
Nicole S. Bryce ◽  
Galina Schevzov ◽  
Vicki Ferguson ◽  
Justin M. Percival ◽  
Jim J.-C. Lin ◽  
...  
Keyword(s):  
Cell Size ◽  
Functional Properties ◽  
Actin Filament ◽  
Actin Filaments ◽  
Myosin Ii ◽  
Molecular Composition ◽  
Cellular Migration ◽  
Stress Fibers ◽  
Human Homologue ◽  
Tropomyosin Isoforms

The specific functions of greater than 40 vertebrate nonmuscle tropomyosins (Tms) are poorly understood. In this article we have tested the ability of two Tm isoforms, TmBr3 and the human homologue of Tm5 (hTM5NM1), to regulate actin filament function. We found that these Tms can differentially alter actin filament organization, cell size, and shape. hTm5NM1was able to recruit myosin II into stress fibers, which resulted in decreased lamellipodia and cellular migration. In contrast, TmBr3 transfection induced lamellipodial formation, increased cellular migration, and reduced stress fibers. Based on coimmunoprecipitation and colocalization studies, TmBr3 appeared to be associated with actin-depolymerizing factor/cofilin (ADF)-bound actin filaments. Additionally, the Tms can specifically regulate the incorporation of other Tms into actin filaments, suggesting that selective dimerization may also be involved in the control of actin filament organization. We conclude that Tm isoforms can be used to specify the functional properties and molecular composition of actin filaments and that spatial segregation of isoforms may lead to localized specialization of actin filament function.

Rac1-GTPase regulates compression-induced actin protrusions (CAPs) of mesenchymal stem cells in 3D collagen micro-tissues

Biomaterials ◽  
2021 ◽  
Vol 274 ◽  
pp. 120829
Author(s):  
Vincent Kwok Lim Lam ◽  
Johnny Yu Hin Wong ◽  
Sing Yian Chew ◽  
Barbara Pui Chan
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Rac1 Gtpase ◽  
3D Collagen ◽  
Actin Protrusions

scholarly journals Quantitative Chemoproteomics for Site-Specific Analysis of Protein Alkylation by 4-Hydroxy-2-Nonenal in Cells

2015 ◽  
Vol 87 (5) ◽  
pp. 2535-2541 ◽  
Author(s):  
Jing Yang ◽  
Keri A. Tallman ◽  
Ned A. Porter ◽  
Daniel C. Liebler
Keyword(s):  
Site Specific ◽  
Specific Analysis ◽  
In Cells

Sodium current function in adult and aged canine atrial cells

2006 ◽  
Vol 291 (2) ◽  
pp. H756-H761 ◽  
Author(s):  
Shigeo Baba ◽  
Wen Dun ◽  
Masanori Hirose ◽  
Penelope A. Boyden
Keyword(s):  
Normal Sinus Rhythm ◽  
Sodium Current ◽  
Cell Voltage ◽  
Current Function ◽  
Structural Remodeling ◽  
Channel Protein ◽  
Normal Sinus ◽  
Atrial Cells ◽  
The Difference ◽  
In Cells

The incidence of atrial fibrillation increases with age, but it is unknown whether there are changes in the intrinsic function of Na+ currents in cells of the aged atria. Thus, we studied right (RA) and left (LA) atrial cells from two groups of dogs, adult and aged (>8 yr), to determine the change in Na+ currents with age. In this study all dogs were in normal sinus rhythm. Whole cell voltage clamp techniques were used to compare the Na+ currents in the two cell groups. Immunocytochemical studies were completed for the Na+ channel protein Nav1.5 to determine whether there was structural remodeling of this protein with age. In cells from aged animals, we found that Na+ currents are similar to those we measured in adult atria. However, Na+ current ( INa) density of the aged atria differed depending on the atrial chamber with LA cell currents being larger than RA cell currents. Thus with age, the difference in INa density between atrial chambers remains. INa kinetic differences between aged and adult cells included a significant acceleration into the inactivated state and an enhanced use-dependent decrease in peak current in aged RA cells. Finally, there is no structural remodeling of the cardiac Na+ channel protein Nav1.5 in the aged atrial cell. In conclusion, with age there is no change in INa density, but there are subtle kinetic differences contributing to slight enhancement of use dependence. There is no structural remodeling of the fast Na+ current protein with age.

scholarly journals The Effect of Aloe Vera Extract to Extensive Lesion and Expression of Transforming Growth Factor (TGF-β) on Alkaline Chemical Trauma Cornea Model

2018 ◽  
Vol 1 (2) ◽  
pp. 1-17
Author(s):  
Fahcreza ◽  
Elsa Iskandar ◽  
Rachmat Hidayat ◽  
Petty Purwanita ◽  
Anang Tribowo ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Wistar Rats ◽  
Aloe Vera ◽  
Control Group ◽  
Treatment Groups ◽  
White Rats ◽  
Significant Difference ◽  
The Difference ◽  
In Cells

Abstract Background: Chemical trauma to the cornea is an emergency condition of the eye that requires early diagnosis and good treatment. Alkaline have ability to saponify fatty acids in cells and cell membranes which can make penetration into the stroma and destroy proteoglycans and collagen in cells. Aloe vera (AV) contains several active substances that are reported to have anti-inflammatory, immunomodulatory, and wound healing effects. AV has been reported to accelerate the healing process of corneal epithelial defects by increasing fibroblast proliferation, collagen production and growth factor production. This study aims to determine the difference between the effect of aloe vera extract with a concentration of 10%, 20%, 40% and BSS on the healing of extensive corneal lesions in white wistar rats alkaline trauma models. Method: This study was an experimental study with a pre and posttest only with control group design in vivo approach to 30 Wistar white rats which were divided into 5 treatment groups for 3 days. Comparative analysis of effectiveness using the ANNOVA test or the Kruskal Wallis test and continued by the post hoc test. Results: Based on the one way ANOVA test there was a statistically significant difference in effectiveness between the five treatment groups on the percentage of corneal wound healing area and TGF-β expression with an assessment of p = 0,000 each. The administration of alloevera (AV) concentration of 20% had a significant difference in percentage of healing of corneal lesions and TGF-β expression compared with other treatment groups with p = 0,000 each. Large differences in the area of corneal lesions in the 40% AV group were -0.45 in the BBS group, 0.146 in the 10% AV group, 0.493 in the 20% AV group. The difference in the AV group 10% was 0.30 in the BBS group, -064 in the AV group 20%, and -0.14 in the AV group 40%. However, TGFβ expression in the normal control group that did not receive treatment was 54.94 (53.21-56-12). TGFβ levels in the BSS group were 10.44, the 10% aloe vera group was 25.43, 47.99 for the 20% aloe vera group and 37.95 for the 40% aloe vera group. Conclusion: There is a difference between the effect of aloe vera extract with concentrations of 10%, 20%, 40% and BSS on the extensive healing of corneal lesions in white wistar rats with alkaline chemical trauma models.

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