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1.
J Cell Biol ; 222(1)2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36219157

RESUMO

Cytokinesis requires the constriction of an actomyosin-based contractile ring and involves multiple F-actin crosslinkers. We show that partial depletion of the C. elegans cytokinetic formin generates contractile rings with low F-actin levels that constrict but are structurally fragile, and we use this background to investigate the roles of the crosslinkers plastin/PLST-1 and ß-heavy-spectrin/SMA-1 during ring constriction. We show that the removal of PLST-1 or SMA-1 has opposite effects on the structural integrity of fragile rings. PLST-1 loss reduces cortical tension that resists ring constriction and makes fragile rings less prone to ruptures and regressions, whereas SMA-1 loss exacerbates structural defects, leading to frequent ruptures and cytokinesis failure. Fragile rings without SMA-1 or containing a shorter SMA-1, repeatedly rupture at the same site, and SMA-1::GFP accumulates at repair sites in fragile rings and in rings cut by laser microsurgery. These results establish that ß-heavy-spectrin stabilizes the constricting ring and reveals the importance of ß-heavy-spectrin size for network connectivity at low F-actin density.


Assuntos
Citoesqueleto de Actina , Citocinese , Espectrina , Actinas , Actomiosina , Animais , Caenorhabditis elegans/citologia , Proteínas de Caenorhabditis elegans/metabolismo , Forminas , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana/metabolismo , Proteínas dos Microfilamentos/metabolismo , Espectrina/metabolismo
2.
Methods Mol Biol ; 2565: 297-309, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36205902

RESUMO

Cultured bovine chromaffin cells have been characterized as a successful model to study changes in the cytoskeleton during the secretory process. In this sense, the distribution and dynamics of the F-actin cytoskeleton can be studied by confocal microscopy using appropriate molecular tools such as LifeAct, a peptide that stains the structures of F-actin. In this work, we describe some methodological protocols making possible to study, under controlled stimulus conditions, the local dynamic changes of F-actin in the cortical zone and also to detect the simultaneous displacements of chromaffin granules and organelles in active zones.


Assuntos
Actinas , Células Cromafins , Citoesqueleto de Actina , Animais , Bovinos , Grânulos Cromafim , Microscopia Confocal/métodos
3.
J Cell Biol ; 222(2)2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36416724

RESUMO

The lipid phosphatidyl-D-myo-inositol-4,5-bisphosphate [PI(4,5)P2] is a master regulator of plasma membrane (PM) function. Its effector proteins regulate transport, signaling, and cytoskeletal processes that define PM structure and function. How a single type of lipid regulates so many parallel processes is unclear. We tested the hypothesis that spatially separate PI(4,5)P2 pools associate with different PM complexes. The mobility of PI(4,5)P2 was measured using biosensors by single-particle tracking. We found that PM lipids including PI(4,5)P2 diffuse rapidly (∼0.3 µm2/s) with Brownian motion, although they spend one third of their time diffusing more slowly. Surprisingly, areas of the PM occupied by PI(4,5)P2-dependent complexes did not slow PI(4,5)P2 lateral mobility. Only the spectrin and septin cytoskeletons showed reduced PI(4,5)P2 diffusion. We conclude that even structures with high densities of PI(4,5)P2 effector proteins, such as clathrin-coated pits and focal adhesions, do not corral unbound PI(4,5)P2, questioning a role for spatially segregated PI(4,5)P2 pools in organizing and regulating PM functions.


Assuntos
Membrana Celular , Lipídeos de Membrana , Fosfatidilinositóis , Citoesqueleto de Actina , Difusão , Espectrina
4.
Life Sci Alliance ; 6(1)2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36288901

RESUMO

We report a case in which sub-stoichiometric binding of an actin-binding protein has profound structural and functional consequences, providing an insight into the fundamental properties of actin regulation. Rng2 is an IQGAP contained in contractile rings in the fission yeast Schizosaccharomyces pombe Here, we used high-speed atomic force microscopy and electron microscopy and found that sub-stoichiometric binding of the calponin-homology actin-binding domain of Rng2 (Rng2CHD) induces global structural changes in skeletal muscle actin filaments, including shortening of the filament helical pitch. Sub-stoichiometric binding of Rng2CHD also reduced the affinity between actin filaments and muscle myosin II carrying ADP and strongly inhibited the motility of actin filaments on myosin II in vitro. On skeletal muscle myosin II-coated surfaces, Rng2CHD stopped the actin movements at a binding ratio of 11%. Rng2CHD also inhibited actin movements on myosin II of the amoeba Dictyostelium, but in this case, by detaching actin filaments from myosin II-coated surfaces. Thus, sparsely bound Rng2CHD induces apparently cooperative structural changes in actin filaments and inhibits force generation by actomyosin II.


Assuntos
Dictyostelium , Schizosaccharomyces , Actinas/metabolismo , Actomiosina/metabolismo , Dictyostelium/metabolismo , Miosinas de Músculo Esquelético/metabolismo , Miosina Tipo II/metabolismo , Citoesqueleto de Actina/metabolismo , Schizosaccharomyces/metabolismo , Proteínas dos Microfilamentos/metabolismo , Proteínas do Citoesqueleto/metabolismo , Difosfato de Adenosina/metabolismo
5.
J Cell Sci ; 136(5)2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36052670

RESUMO

In common with other actomyosin contractile cellular machineries, actin turnover is required for normal function of the cytokinetic contractile ring. Cofilin is an actin-binding protein contributing to turnover by severing actin filaments, required for cytokinesis by many organisms. In fission yeast cofilin mutants, contractile rings suffer bridging instabilities in which segments of the ring peel away from the plasma membrane, forming straight bridges whose ends remain attached to the membrane. The origin of bridging instability is unclear. Here, we used molecularly explicit simulations of contractile rings to examine the role of cofilin. Simulations reproduced the experimentally observed cycles of bridging and reassembly during constriction, and the occurrence of bridging in ring segments with low density of the myosin II protein Myo2. The lack of cofilin severing produced ∼2-fold longer filaments and, consequently, ∼2-fold higher ring tensions. Simulations identified bridging as originating in the boosted ring tension, which increased centripetal forces that detached actin from Myo2, which was anchoring actin to the membrane. Thus, cofilin serves a critical role in cytokinesis by providing protection from bridging, the principal structural threat to contractile rings.


Assuntos
Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Citoesqueleto de Actina/metabolismo , Fatores de Despolimerização de Actina/metabolismo , Actinas/metabolismo , Actomiosina/metabolismo , Citocinese , Proteínas dos Microfilamentos/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Miosina Tipo II/genética , Miosina Tipo II/metabolismo , Schizosaccharomyces/genética , Schizosaccharomyces/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Proteínas de Schizosaccharomyces pombe/metabolismo
6.
J Ethnopharmacol ; 301: 115737, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36179952

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine herb Celastrus orbiculatus Thunb. is an important folk medicinal plant in China that has been used as an anti-inflammatory, antitumor, and analgesic in various diseases. Recent years, many studies have reported the significant effects of Celastrus orbiculatus Thunb. extract (COE) on gastric cancer. However, the specific mechanism by which COE regulates gastric cancer cytoskeleton remodeling and thus inhibits EMT has not yet been reported. AIM OF STUDY: To study the effect and mechanism of COE in inhibiting the epithelial-mesenchymal transition (EMT) and metastasis of gastric cancer cells, laying an experimental foundation for the clinical application and further development of COE. METHODS: The high-content cell dynamic tracking system was used to continuously track the trajectory of cell movement in real time. Through the high-content data, the average movement distance and movement speed of the cells are calculated. Additionally, the dynamic images of the cell movement in the high-content imaging system are derived to analyze the impact of COE on the movement of gastric cancer cells. Cytoskeleton staining experiment was performed to detect the effect of COE on the assembly of gastric cancer cell cytoskeleton proteins. Western blot was employed to detect the changes of EMT and metastasis-related proteins in the gastric cancer cells treated by COE. The effect of COE on the key regulatory protein Cofilin-1 (CFL1) of cell movement was examined by Western blot and protein degradation experiment. The effect of COE on EMT and metastasis of the gastric cancer cells lacking CFL1 was assessed by a transwell assay. The in vivo inhibitory effect of COE on EMT and metastasis of gastric cancer was determined by the animal living image system. IHC assays were used to detect the levels of EMT-related proteins in COE reversal in vivo. RESULT: The results showed that the movement distance and average movement speed of gastric cancer cells after COE treatment were significantly lower than those of the control group. Cytoskeleton staining experiments revealed that COE can significantly change the distribution of skeletal proteins in gastric cancer cells. Additionally, COE treatment significantly reduced the expression of Matrix metalloproteinases (MMP-2, MMP-9) and other proteins. Furthermore, COE can significantly accelerate the degradation of CFL1 protein, and both COE treatment and CFL1 deletion can significantly inhibit EMT and metastasis of gastric cancer cells. Lastly, the number of peritoneal metastases of gastric cancer cells was significantly reduced in animals after COE treatment. COE can reverse the levels of EMT-related proteins while reducing the expression levels of CFL1 protein in vivo. CONCLUSION: COE can significantly inhibit EMT and metastasis of gastric cancer cells in vivo and in vitro. This effect may be achieved by reducing the stability of CFL1 and inhibiting the assembly of actin in gastric cancer cells.


Assuntos
Celastrus , Neoplasias Gástricas , Animais , Transição Epitelial-Mesenquimal , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Cofilina 1/farmacologia , Linhagem Celular Tumoral , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Movimento Celular , Citoesqueleto de Actina
7.
Proc Natl Acad Sci U S A ; 119(49): e2206159119, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36442097

RESUMO

Morphogenesis of active shells such as cells is a fundamental chemomechanical process that often exhibits three-dimensional (3D) large deformations and chemical pattern dynamics simultaneously. Here, we establish a chemomechanical active shell theory accounting for mechanical feedback and biochemical regulation to investigate the symmetry-breaking and 3D chiral morphodynamics emerging in the cell cortex. The active bending and stretching of the elastic shells are regulated by biochemical signals like actomyosin and RhoA, which, in turn, exert mechanical feedback on the biochemical events via deformation-dependent diffusion and inhibition. We show that active deformations can trigger chemomechanical bifurcations, yielding pulse spiral waves and global oscillations, which, with increasing mechanical feedback, give way to traveling or standing waves subsequently. Mechanical feedback is also found to contribute to stabilizing the polarity of emerging patterns, thus ensuring robust morphogenesis. Our results reproduce and unravel the experimentally observed solitary and multiple spiral patterns, which initiate asymmetric cleavage in Xenopus and starfish embryogenesis. This study underscores the crucial roles of mechanical feedback in cell development and also suggests a chemomechanical framework allowing for 3D large deformation and chemical signaling to explore complex morphogenesis in living shell-like structures.


Assuntos
Fenômenos Químicos , Citoesqueleto de Actina , Actomiosina , Diferenciação Celular , Físico-Química , Morfogênese
8.
Sci Rep ; 12(1): 20515, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36443454

RESUMO

The formins constitute a large class of multi-domain polymerases that catalyze the localization and growth of unbranched actin filaments in cells from yeast to mammals. The conserved FH2 domains form dimers that bind actin at the barbed end of growing filaments and remain attached as new subunits are added. Profilin-actin is recruited and delivered to the barbed end by formin FH1 domains via the binding of profilin to interspersed tracts of poly-L-proline. We present a structural model showing that profilin-actin can bind the FH2 dimer at the barbed end stabilizing a state where profilin prevents its associated actin subunit from directly joining the barbed end. It is only with the dissociation of profilin from the polymerase that an actin subunit rotates and docks into its helical position, consistent with observations that under physiological conditions optimal elongation rates depend on the dissociation rate of profilin, independently of cellular concentrations of actin subunits.


Assuntos
Actinas , Profilinas , Animais , Forminas , Citoesqueleto de Actina , Modelos Estruturais , Nucleotidiltransferases , Polímeros , Saccharomyces cerevisiae , Mamíferos
12.
Nat Commun ; 13(1): 7089, 2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36402771

RESUMO

The formation and recovery of gaps in the vascular endothelium governs a wide range of physiological and pathological phenomena, from angiogenesis to tumor cell extravasation. However, the interplay between the mechanical and signaling processes that drive dynamic behavior in vascular endothelial cells is not well understood. In this study, we propose a chemo-mechanical model to investigate the regulation of endothelial junctions as dependent on the feedback between actomyosin contractility, VE-cadherin bond turnover, and actin polymerization, which mediate the forces exerted on the cell-cell interface. Simulations reveal that active cell tension can stabilize cadherin bonds, but excessive RhoA signaling can drive bond dissociation and junction failure. While actin polymerization aids gap closure, high levels of Rac1 can induce junction weakening. Combining the modeling framework with experiments, our model predicts the influence of pharmacological treatments on the junction state and identifies that a critical balance between RhoA and Rac1 expression is required to maintain junction stability. Our proposed framework can help guide the development of therapeutics that target the Rho family of GTPases and downstream active mechanical processes.


Assuntos
Actinas , Células Endoteliais , Células Endoteliais/metabolismo , Actinas/metabolismo , Retroalimentação , Transdução de Sinais , Citoesqueleto de Actina/metabolismo
13.
Proc Natl Acad Sci U S A ; 119(48): e2209441119, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36409887

RESUMO

Skeletal muscle force production is increased at longer compared to shorter muscle lengths because of length-dependent priming of thick filament proteins in the contractile unit before contraction. Using small-angle X-ray diffraction in combination with a mouse model that specifically cleaves the stretch-sensitive titin protein, we found that titin cleavage diminished the length-dependent priming of the thick filament. Strikingly, a titin-sensitive, length-dependent priming was also present in thin filaments, which seems only possible via bridge proteins between thick and thin filaments in resting muscle, potentially myosin-binding protein C. We further show that these bridges can be forcibly ruptured via high-speed stretches. Our results advance a paradigm shift to the fundamental regulation of length-dependent priming, with titin as the key driver.


Assuntos
Citoesqueleto de Actina , Sarcômeros , Camundongos , Animais , Conectina/metabolismo , Sarcômeros/metabolismo , Citoesqueleto de Actina/metabolismo , Contração Muscular/fisiologia , Músculo Esquelético/metabolismo , Proteínas Quinases/metabolismo
14.
Sci Rep ; 12(1): 19993, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36411303

RESUMO

Total-internal reflection fluorescence (TIRF) microscope is a unique technique for selective excitation of only those fluorophore molecules in a cellular environment, which are located at the sub-diffraction axial distance of a cell's contact-area. Despite this prominent feature of the TIRF microscope, making quantitative use of this technique has been a challenge, since the excitation intensity strongly depends on the axial position of a fluorophore molecule. Here, we present an easy-implemented data analysis method to quantitatively characterize the fluorescent signal, without considering the intensity-value. We use F-actin patches in single-melanoma cells as an example and define two quantities of elongation and surface density for F-actin patches at the contact-area of a melanoma cell. The elongation parameter can evaluate the dispersion of F-actin patches at the contact-area of a cell and is useful to classify the attaching, spreading, and expanding stages of a cell. Following that, we present the profile of the surface density of F-actin patches as a quantity to probe the spatio-temporal distribution of the F-actin patches at the contact-area of a cell. The data analysis methods that are proposed here will also be applicable in the image analysis of the other advanced optical microscopic methods.


Assuntos
Actinas , Melanoma , Humanos , Actinas/metabolismo , Microscopia de Fluorescência/métodos , Citoesqueleto de Actina/metabolismo , Processamento de Imagem Assistida por Computador/métodos , Corantes Fluorescentes
15.
Biomed Pharmacother ; 156: 113920, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36411613

RESUMO

Renal injury and the development of albuminuria are tightly connected with the loss of podocytes. Podocyte damages cause proteinuric renal diseases since podocyte foot processes (FP) and their interposed slit diaphragms (SD) are the final barriers against protein loss. Podocyte effacement and the resultant deterioration of podocyte SD integrity that involve the active rearrangement of the podocyte actin cytoskeleton is a chief mechanism of proteinuric kidney diseases. The progress of these injuries can eventually lead to cell detachment and death. Due to the prominence of the actin cytoskeleton in maintaining glomerular filtration, the assessment of the molecular design and regulation of actin is a central target of podocyte research. In the current review, a comprehensive summary of the actin cytoskeleton, its constituents, and regulatory signaling pathways has been provided. Since actin-regulated cell plasticity is a crucial feature of normal podocyte function, and deteriorations in its dynamics seem to directly affect podocyte morphology and glomerular permeability, this review discusses cascades that regulate actin polymerization in podocytes.


Assuntos
Actinas , Podócitos , Citoesqueleto de Actina , Glomérulos Renais , Junções Intercelulares
16.
Nat Commun ; 13(1): 7008, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36385016

RESUMO

Active stresses are generated and transmitted throughout diverse F-actin architectures within the cell cytoskeleton, and drive essential behaviors of the cell, from cell division to migration. However, while the impact of F-actin architecture on the transmission of stress is well studied, the role of architecture on the ab initio generation of stresses remains less understood. Here, we assemble F-actin networks in vitro, whose architectures are varied from branched to bundled through F-actin nucleation via Arp2/3 and the formin mDia1. Within these architectures, we track the motions of embedded myosin thick filaments and connect them to the extent of F-actin network deformation. While mDia1-nucleated networks facilitate the accumulation of stress and drive contractility through enhanced actomyosin sliding, branched networks prevent stress accumulation through the inhibited processivity of thick filaments. The reduction in processivity is due to a decrease in translational and rotational motions constrained by the local density and geometry of F-actin.


Assuntos
Citoesqueleto de Actina , Actinas , Actomiosina , Forminas , Miosinas
17.
PLoS One ; 17(11): e0276584, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36378629

RESUMO

Homeostasis between platelet production and clearance is essential for human health. A critical facet of the balance that facilitates platelet clearance from the circulation is apoptosis (programmed cell death). The precise cellular mechanisms that underpin platelet apoptosis are not defined. In nucleated cells, reorganization of the actin cytoskeleton is known to regulate platelet apoptosis. However, the role of the actin cytoskeleton in regulating apoptosis in platelets has not been extensively studied as they are anucleate and exhibit a distinctive physiology. Here, apoptosis was induced in washed human platelets using ABT-737, a BH3-mimetic drug. Mitochondrial depolarization was measured using the ratiometric dye JC-1; surface phosphatidylserine (PS) exposure was measured by annexin V binding; caspase-3 activation was measured by Western blotting. All three apoptotic markers were unaffected by the presence of either the actin depolymerizing drug cytochalasin D or the actin polymerizing drug jasplakinolide. Moreover, platelets were isolated from wild-type (WT) mice and mice deficient in gelsolin (Gsn), an actin-binding protein that is essential for normal cytoskeletal remodeling. In response to ABT-737, gelsolin-null (Gsn-/-) platelets initially showed accelerated PS exposure relative to WT platelets, however, both WT and Gsn-/- platelets exhibited similar levels of mitochondrial depolarization and caspase-3 activation in response to ABT-737. We conclude that ABT-737 induces established markers of platelet apoptosis in an actin-independent manner.


Assuntos
Actinas , Gelsolina , Humanos , Camundongos , Animais , Caspase 3/metabolismo , Gelsolina/metabolismo , Actinas/metabolismo , Plaquetas/metabolismo , Apoptose/fisiologia , Fosfatidilserinas/metabolismo , Citoesqueleto de Actina/metabolismo
18.
J Gen Physiol ; 154(12)2022 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-36327149

RESUMO

Classically, striated muscle contraction is initiated by calcium (Ca2+)-dependent structural changes in regulatory proteins on actin-containing thin filaments, which allow the binding of myosin motors to generate force. Additionally, dynamic switching between resting off and active on myosin states has been shown to regulate muscle contractility, a recently validated mechanism by novel myosin-targeted therapeutics. The molecular nature of this switching, however, is not understood. Here, using a combination of small-angle x-ray fiber diffraction and biochemical assays with reconstituted systems, we show that cardiac thick filaments are directly Ca2+-regulated. We find that Ca2+ induces a structural transition of myosin heads from ordered off states close to the thick filament to disordered on states closer to the thin filaments. Biochemical assays show a Ca2+-induced transition from an inactive super-relaxed (SRX) state(s) to an active disordered-relaxed (DRX) state(s) in synthetic thick filaments. We show that these transitions are an intrinsic property of cardiac myosin only when assembled into thick filaments and provide a fresh perspective on nature's two orthogonal mechanisms to regulate muscle contraction through the thin and the thick filaments.


Assuntos
Cálcio , Miosinas Cardíacas , Cálcio/metabolismo , Miosinas Cardíacas/metabolismo , Citoesqueleto de Actina/metabolismo , Miosinas/metabolismo , Sarcômeros/metabolismo
19.
PLoS Pathog ; 18(11): e1010656, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36374839

RESUMO

Pore-forming proteins (PFPs) comprise the largest single class of bacterial protein virulence factors and are expressed by many human and animal bacterial pathogens. Cells that are attacked by these virulence factors activate epithelial intrinsic cellular defenses (or INCEDs) to prevent the attendant cellular damage, cellular dysfunction, osmotic lysis, and organismal death. Several conserved PFP INCEDs have been identified using the nematode Caenorhabditis elegans and the nematicidal PFP Cry5B, including mitogen-activated protein kinase (MAPK) signaling pathways. Here we demonstrate that the gene nck-1, which has homologs from Drosophila to humans and links cell signaling with localized F-actin polymerization, is required for INCED against small-pore PFPs in C. elegans. Reduction/loss of nck-1 function results in C. elegans hypersensitivity to PFP attack, a hallmark of a gene required for INCEDs against PFPs. This requirement for nck-1-mediated INCED functions cell-autonomously in the intestine and is specific to PFPs but not to other tested stresses. Genetic interaction experiments indicate that nck-1-mediated INCED against PFP attack is independent of the major MAPK PFP INCED pathways. Proteomics and cell biological and genetic studies further indicate that nck-1 functions with F-actin cytoskeleton modifying genes like arp2/3, erm-1, and dbn-1 and that nck-1/arp2/3 promote pore repair at the membrane surface and protect against PFP attack independent of p38 MAPK. Consistent with these findings, PFP attack causes significant changes in the amount of actin cytoskeletal proteins and in total amounts of F-actin in the target tissue, the intestine. nck-1 mutant animals appear to have lower F-actin levels than wild-type C. elegans. Studies on nck-1 and other F-actin regulating proteins have uncovered a new and important role of this pathway and the actin cytoskeleton in PFP INCED and protecting an intestinal epithelium in vivo against PFP attack.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Humanos , Caenorhabditis elegans/microbiologia , Actinas/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Fatores de Virulência/metabolismo , Porinas/metabolismo , Citoesqueleto de Actina/metabolismo
20.
Biol Open ; 11(12)2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36444960

RESUMO

Actin, one of the most abundant intracellular proteins in mammalian cells, is a critical regulator of cell shape and polarity, migration, cell division, and transcriptional response. Angiogenesis, or the formation of new blood vessels in the body is a well-coordinated multi-step process. Endothelial cells lining the blood vessels acquire several new properties such as front-rear polarity, invasiveness, rapid proliferation and motility during angiogenesis. This is achieved by changes in the regulation of the actin cytoskeleton. Actin remodelling underlies the switch between the quiescent and angiogenic state of the endothelium. Actin forms endothelium-specific structures that support uniquely endothelial functions. Actin regulators at endothelial cell-cell junctions maintain the integrity of the blood-tissue barrier while permitting trans-endothelial leukocyte migration. This review focuses on endothelial actin structures and less-recognised actin-mediated endothelial functions. Readers are referred to other recent reviews for the well-recognised roles of actin in endothelial motility, barrier functions and leukocyte transmigration. Actin generates forces that are transmitted to the extracellular matrix resulting in vascular matrix remodelling. In this review, we attempt to synthesize our current understanding of the roles of actin in vascular morphogenesis. We speculate on the vascular bed specific differences in endothelial actin regulation and its role in the vast heterogeneity in endothelial morphology and function across the various tissues of our body.


Assuntos
Actinas , Células Endoteliais , Animais , Citoesqueleto de Actina , Movimento Celular , Morfogênese , Mamíferos
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