scholarly journals FAM83G/PAWS1 controls cytoskeletal dynamics and cell migration through association with the SH3 adaptor CD2AP

2017 ◽  
Author(s):  
Timothy D. Cummins ◽  
Kevin Z. L. Wu ◽  
Polyxeni Bozatzi ◽  
Kevin S. Dingwell ◽  
Thomas Macartney ◽  
...  
Keyword(s):  
Cell Migration ◽  
Live Cell Imaging ◽  
Focal Adhesions ◽  
Cellular Migration ◽  
Actin Organization ◽  
Actin Stress Fibre ◽  
Fibre Network ◽  
Cytoskeletal Dynamics ◽  
Summary Statement ◽  
Bmp Signalling

AbstractOur previous studies of PAWS1 (Protein Associated With SMAD1) have suggested that this molecule has roles beyond BMP signalling. To investigate these roles, we have used CRISPR/Cas9 to generate PAWS1 knockout cells. Here, we show that PAWS1 plays a role in the regulation of the cytoskeletal machinery, including actin and focal adhesion dynamics, and cell migration. Confocal microscopy and live cell imaging of actin in U2OS cells indicate that PAWS1 is also involved in cytoskeletal dynamics and organization. Loss of PAWS1 causes severe defects in F-actin organization and distribution as well as in lamellipodial organization, resulting in impaired cell migration. PAWS1 interacts in a dynamic fashion with the actin/cytoskeletal regulator CD2AP at lamellae, suggesting that its association with CD2AP controls actin organization and cellular migration.Summary statementPAWS1/FAM83G controls cell migration by influencing the organisation of F-actin and focal adhesions and the distribution of the actin stress fibre network through its association with CD2AP.

scholarly journals Integrins traffic rapidly via circular dorsal ruffles and macropinocytosis during stimulated cell migration

2011 ◽  
Vol 193 (1) ◽  
pp. 61-70 ◽  
Author(s):  
Zhizhan Gu ◽  
Erika H. Noss ◽  
Victor W. Hsu ◽  
Michael B. Brenner
Keyword(s):  
Functional Analysis ◽  
Cell Migration ◽  
Growth Factor ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Focal Adhesions ◽  
Initial Step ◽  
Ventral Surface ◽  
Platelet Derived Growth Factor ◽  
Trailing Edges

During cell migration, integrins are redistributed from focal adhesions undergoing disassembly at the cell’s trailing edges to new focal adhesions assembling at leading edges. The initial step of integrin redistribution is thought to require clathrin-mediated endocytosis. However, whether clathrin-mediated endocytosis functions in different contexts, such as basal versus stimulated migration, has not been determined. In this paper, we examine the spatial and temporal redistribution of integrins from focal adhesions upon stimulation by growth factors. Four-dimensional confocal live-cell imaging along with functional analysis reveals that surface integrins do not undergo significant endocytosis at ventral focal adhesions upon cell stimulation with the platelet-derived growth factor. Rather, they abruptly redistribute to dorsal circular ruffles, where they are internalized through macropinocytosis. The internalized integrins then transit through recycling endosomal compartments to repopulate newly formed focal adhesions on the ventral surface. These findings explain why integrins have long been observed to redistribute through both surface-based and internal routes and identify a new function for macropinocytosis during growth factor–induced cell migration.

scholarly journals The Activity of Kv 11.1 Potassium Channel Modulates F-Actin Organization During Cell Migration of Pancreatic Ductal Adenocarcinoma Cells

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 135 ◽  
Author(s):  
Sagar Manoli ◽  
Stefano Coppola ◽  
Claudia Duranti ◽  
Matteo Lulli ◽  
Lara Magni ◽  
...  
Keyword(s):  
Cell Migration ◽  
Potassium Channel ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Actin Polymerization ◽  
Focal Adhesions ◽  
Stress Fibers ◽  
Pancreatic Stellate Cells ◽  
Ductal Adenocarcinoma ◽  
Actin Organization ◽  
Cells Cultured

Cell migration exerts a pivotal role in tumor progression, underlying cell invasion and metastatic spread. The cell migratory program requires f-actin re-organization, generally coordinated with the assembly of focal adhesions. Ion channels are emerging actors in regulating cell migration, through different mechanisms. We studied the role of the voltage dependent potassium channel KV 11.1 on cell migration of pancreatic ductal adenocarcinoma (PDAC) cells, focusing on its effects on f-actin organization and dynamics. Cells were cultured either on fibronectin (FN) or on a desmoplastic matrix (DM) with the addition of a conditioned medium produced by pancreatic stellate cells (PSC) maintained in hypoxia (Hypo-PSC-CM), to better mimic the PDAC microenvironment. KV11.1 was essential to maintain stress fibers in a less organized arrangement in cells cultured on FN. When PDAC cells were cultured on DM plus Hypo-PSC-CM, KV11.1 activity determined the organization of cortical f-actin into sparse and long filopodia, and allowed f-actin polymerization at a high speed. In both conditions, blocking KV11.1 impaired PDAC cell migration, and, on cells cultured onto FN, the effect was accompanied by a decrease of basal intracellular Ca2+ concentration. We conclude that KV11.1 is implicated in sustaining pro-metastatic signals in pancreatic cancer, through a reorganization of f-actin in stress fibers and a modulation of filopodia formation and dynamics.

scholarly journals Actin stress fibre subtypes in mesenchymal-migrating cells

Open Biology ◽  
2013 ◽  
Vol 3 (6) ◽  
pp. 130001 ◽  
Author(s):  
Tea Vallenius
Keyword(s):  
Cell Migration ◽  
Myosin Ii ◽  
Focal Adhesions ◽  
Mesenchymal Cell ◽  
Molecular Composition ◽  
Current View ◽  
Stress Fibre ◽  
Actin Stress Fibre ◽  
Extracellular Matrix Remodelling ◽  
Migrating Cells

Mesenchymal cell migration is important for embryogenesis and tissue regeneration. In addition, it has been implicated in pathological conditions such as the dissemination of cancer cells. A characteristic of mesenchymal-migrating cells is the presence of actin stress fibres, which are thought to mediate myosin II-based contractility in close cooperation with associated focal adhesions. Myosin II-based contractility regulates various cellular activities, which occur in a spatial and temporal manner to achieve directional cell migration. These myosin II-based activities involve the maturation of integrin-based adhesions, generation of traction forces, establishment of the front-to-back polarity axis, retraction of the trailing edge, extracellular matrix remodelling and mechanotransduction. Growing evidence suggests that actin stress fibre subtypes, namely dorsal stress fibres, transverse arcs and ventral stress fibres, could provide this spatial and temporal myosin II-based activity. Consistent with their functional differences, recent studies have demonstrated that the molecular composition of actin stress fibre subtypes differ significantly. This present review focuses on the current view of the molecular composition of actin stress fibre subtypes and how these fibre subtypes regulate mesenchymal cell migration.

scholarly journals Zyxin Is Involved in Fibroblast Rigidity Sensing and Durotaxis

2021 ◽  
Vol 9 ◽  
Author(s):  
Ai Kia Yip ◽  
Songjing Zhang ◽  
Lor Huai Chong ◽  
Elsie Cheruba ◽  
Jessie Yong Xing Woon ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Actin Cytoskeleton ◽  
Focal Adhesions ◽  
Wild Type ◽  
Actin Organization ◽  
Rigidity Sensing ◽  
Substrate Rigidity ◽  
Cell Traction ◽  
Traction Stress

Focal adhesions (FAs) are specialized structures that enable cells to sense their extracellular matrix rigidity and transmit these signals to the interior of the cells, bringing about actin cytoskeleton reorganization, FA maturation, and cell migration. It is known that cells migrate towards regions of higher substrate rigidity, a phenomenon known as durotaxis. However, the underlying molecular mechanism of durotaxis and how different proteins in the FA are involved remain unclear. Zyxin is a component of the FA that has been implicated in connecting the actin cytoskeleton to the FA. We have found that knocking down zyxin impaired NIH3T3 fibroblast’s ability to sense and respond to changes in extracellular matrix in terms of their FA sizes, cell traction stress magnitudes and F-actin organization. Cell migration speed of zyxin knockdown fibroblasts was also independent of the underlying substrate rigidity, unlike wild type fibroblasts which migrated fastest at an intermediate substrate rigidity of 14 kPa. Wild type fibroblasts exhibited durotaxis by migrating toward regions of increasing substrate rigidity on polyacrylamide gels with substrate rigidity gradient, while zyxin knockdown fibroblasts did not exhibit durotaxis. Therefore, we propose zyxin as an essential protein that is required for rigidity sensing and durotaxis through modulating FA sizes, cell traction stress and F-actin organization.

scholarly journals Increased Lamin B1 Levels Promote Cell Migration by Altering Perinuclear Actin Organization

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2161
Author(s):  
Andrea Fracchia ◽  
Tal Asraf ◽  
Mali Salmon-Divon ◽  
Gabi Gerlitz
Keyword(s):  
Cell Migration ◽  
Actin Filaments ◽  
Migration Rate ◽  
Tumor Formation ◽  
Cellular Migration ◽  
Lamin A ◽  
Linc Complex ◽  
Actin Organization ◽  
Lamin B1 ◽  
Promote Cell Migration

Cell migration requires reposition and reshaping of the cell nucleus. The nuclear lamina is highly important for migration of both primary and cancer cells. B-type lamins are important for proper migration of epicardial cells and neurons and increased lamin B to lamin A ratio accelerates cancer cell migration through confined spaces. Moreover, a positive association between lamin B1 levels and tumor formation and progression is found in various cancer types. Still, the molecular mechanism by which B-type lamins promote cell migration is not fully understood. To better understand this mechanism, we tested the effects of lamin B1 on perinuclear actin organization. Here we show that induction of melanoma cell migration leads to the formation of a cytosolic Linker of Nucleoskeleton and Cytoskeleton (LINC) complex-independent perinuclear actin rim, which has not been detected in migrating cells, yet. Significantly, increasing the levels of lamin B1 but not the levels of lamin A prevented perinuclear actin rim formation while accelerated the cellular migration rate. To interfere with the perinuclear actin rim, we generated a chimeric protein that is localized to the outer nuclear membrane and cleaves perinuclear actin filaments in a specific manner without disrupting other cytosolic actin filaments. Using this tool, we found that disruption of the perinuclear actin rim accelerated the cellular migration rate in a similar manner to lamin B1 over-expression. Taken together, our results suggest that increased lamin B1 levels can accelerate cell migration by inhibiting the association of the nuclear envelope with actin filaments that may reduce nuclear movement and deformability.

Cytoskeletal control of nuclear morphology and stiffness are required for OPN-induced bone-marrow-derived mesenchymal stem cell migration

2019 ◽  
Vol 97 (4) ◽  
pp. 463-470 ◽  
Author(s):  
Lingling Liu ◽  
Qing Luo ◽  
Jinghui Sun ◽  
Guanbin Song
Keyword(s):  
Bone Marrow ◽  
Cell Migration ◽  
Actin Cytoskeleton ◽  
Cytochalasin D ◽  
Actin Assembly ◽  
Projected Area ◽  
Actin Organization ◽  
Nuclear Mechanics ◽  
Stem Cell Migration ◽  
Cytoskeletal Dynamics

During cell migration, the movement of the nucleus must be coordinated with the cytoskeletal dynamics that influence the efficiency of cell migration. Our previous study demonstrated that osteopontin (OPN) significantly promotes the migration of bone-marrow-derived mesenchymal stem cells (BMSCs). However, the mechanism that regulates nuclear mechanics of the cytoskeleton during OPN-promoted BMSC migration remains unclear. In this study, we investigated how the actin cytoskeleton influences nuclear mechanics in BMSCs. We assessed the morphology and mechanics of the nuclei in the OPN-treated BMSCs subjected to disruption or polymerization of the actin cytoskeleton. We found that disruption of actin organization by cytochalasin D (Cyto D) resulted in a decrease in the nuclear projected area and nuclear stiffness. Stabilizing the actin assembly with jasplakinolide (JASP) resulted in an increase in the nuclear projected area and nuclear stiffness. SUN1 (Sad-1/UNC-84 1) is a component of the LINC (linker of nucleoskeleton and cytoskeleton) complex involved in the connections between the nucleus and the cytoskeleton. We found that SUN1 depletion by RNAi decreased the nuclear stiffness and OPN-promoted BMSC migration. Thus, the F-actin cytoskeleton plays an important role in determining the morphology and mechanical properties of the nucleus. We suggest that the cytoskeletal–nuclear interconnectivity through SUN1 proteins plays an important role in OPN-promoted BMSC migration.

scholarly journals Musashi-1 Enhances Glioblastoma Cell Migration and Cytoskeletal Dynamics through Translational Inhibition of Tensin3

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Hsiao-Yun Chen ◽  
Liang-Ting Lin ◽  
Mong-Lien Wang ◽  
Benoit Laurent ◽  
Chih-Hung Hsu ◽  
...  
Keyword(s):  
Cell Migration ◽  
Glioblastoma Cell ◽  
Cytoskeletal Dynamics ◽  
Translational Inhibition
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