scholarly journals Essential role of MARCKS in cortical actin dynamics during gastrulation movements

2004 ◽  
Vol 164 (2) ◽  
pp. 169-174 ◽  
Author(s):  
Hidekazu Iioka ◽  
Naoto Ueno ◽  
Noriyuki Kinoshita
Keyword(s):  
Wnt Pathway ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Convergent Extension ◽  
Embryonic Cells ◽  
Cortical Actin ◽  
Morphogenetic Movements ◽  
Kinase Substrate ◽  
Cytoskeletal Regulation

Myristoylated alanine-rich C kinase substrate (MARCKS) is an actin-binding, membrane-associated protein expressed during Xenopus embryogenesis. We analyzed its function in cytoskeletal regulation during gastrulation. Here, we show that blockade of its function impaired morphogenetic movements, including convergent extension. MARCKS was required for control of cell morphology, motility, adhesion, protrusive activity, and cortical actin formation in embryonic cells. We also demonstrate that the noncanonical Wnt pathway promotes the formation of lamellipodia- and filopodia-like protrusions and that MARCKS is necessary for this activity. These findings show that MARCKS regulates the cortical actin formation that is requisite for dynamic morphogenetic movements.

scholarly journals α-Catenin–mediated cadherin clustering couples cadherin and actin dynamics

2015 ◽  
Vol 210 (4) ◽  
pp. 647-661 ◽  
Author(s):  
Chi-Shuo Chen ◽  
Soonjin Hong ◽  
Indrajyoti Indra ◽  
Alina P. Sergeeva ◽  
Regina B. Troyanovsky ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Molecular Mechanism ◽  
Point Mutations ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Cortical Actin ◽  
Actin Binding Domain ◽  
Cell Adhesive ◽  
Cis And Trans

The function of the actin-binding domain of α-catenin, αABD, including its possible role in the direct anchorage of the cadherin–catenin complex to the actin cytoskeleton, has remained uncertain. We identified two point mutations on the αABD surface that interfere with αABD binding to actin and used them to probe the role of α-catenin–actin interactions in adherens junctions. We found that the junctions directly bound to actin via αABD were more dynamic than the junctions bound to actin indirectly through vinculin and that recombinant αABD interacted with cortical actin but not with actin bundles. This interaction resulted in the formation of numerous short-lived cortex-bound αABD clusters. Our data suggest that αABD clustering drives the continuous assembly of transient, actin-associated cadherin–catenin clusters whose disassembly is maintained by actin depolymerization. It appears then that such actin-dependent αABD clustering is a unique molecular mechanism mediating both integrity and reassembly of the cell–cell adhesive interface formed through weak cis- and trans-intercadherin interactions.

scholarly journals Focus on ADF/Cofilin: Beyond Actin Cytoskeletal Regulation

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Cheng-Han Tsai ◽  
Yi-Jang Lee
Keyword(s):  
Cell Cycle ◽  
Signaling Pathway ◽  
Small Gtpase ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Biological Functions ◽  
Lim Kinase ◽  
Cytoskeletal Regulation ◽  
Pathophysiological Role

Actin depolymerizing factor (ADF)/cofilin, an actin-binding protein ubiquitously expressed in a variety of organisms, is required for regulation of actin dynamics. The activity of ADF/cofilin is dependent on serine 3 phosphorylation by LIM kinase (LIMK), which is regulated by the Rho small GTPase signaling pathway. ADF/cofilin is strongly associated with several important cell biological functions, including cell cycle, morphological maintenance, and locomotion. These functions affect several biological events, including embryogenesis, oncology, nephropathy, and neurodegenerations. Here, we focus on the biochemical and pathophysiological role of ADF/cofilin in mammals.

scholarly journals The Two ADF-H Domains of Twinfilin Play Functionally Distinct Roles in Interactions with Actin Monomers

2002 ◽  
Vol 13 (11) ◽  
pp. 3811-3821 ◽  
Author(s):  
Pauli J. Ojala ◽  
Ville O. Paavilainen ◽  
Maria K. Vartiainen ◽  
Roman Tuma ◽  
Alan G. Weeds ◽  
...  
Keyword(s):  
Binding Site ◽  
Binding Activity ◽  
Size Exclusion ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Actin Monomer ◽  
Wild Type ◽  
Native Page ◽  
Exclusion Chromatography

Twinfilin is a ubiquitous and abundant actin monomer–binding protein that is composed of two ADF-H domains. To elucidate the role of twinfilin in actin dynamics, we examined the interactions of mouse twinfilin and its isolated ADF-H domains with G-actin. Wild-type twinfilin binds ADP-G-actin with higher affinity (K D = 0.05 μM) than ATP-G-actin (K D = 0.47 μM) under physiological ionic conditions and forms a relatively stable (k off = 1.8 s−1) complex with ADP-G-actin. Data from native PAGE and size exclusion chromatography coupled with light scattering suggest that twinfilin competes with ADF/cofilin for the high-affinity binding site on actin monomers, although at higher concentrations, twinfilin, cofilin, and actin may also form a ternary complex. By systematic deletion analysis, we show that the actin-binding activity is located entirely in the two ADF-H domains of twinfilin. Individually, these domains compete for the same binding site on actin, but the C-terminal ADF-H domain, which has >10-fold higher affinity for ADP-G-actin, is almost entirely responsible for the ability of twinfilin to increase the amount of monomeric actin in cosedimentation assays. Isolated ADF-H domains associate with ADP-G-actin with rapid second-order kinetics, whereas the association of wild-type twinfilin with G-actin exhibits kinetics consistent with a two-step binding process. These data suggest that the association with an actin monomer induces a first-order conformational change within the twinfilin molecule. On the basis of these results, we propose a kinetic model for the role of twinfilin in actin dynamics and its possible function in cells.

scholarly journals Wnt5b integrates Fak1a to mediate gastrulation cell movements via Rac1 and Cdc42

Open Biology ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 190273
Author(s):  
I-Chen Hung ◽  
Tsung-Ming Chen ◽  
Jing-Ping Lin ◽  
Yu-Ling Tai ◽  
Tang-Long Shen ◽  
...  
Keyword(s):  
Focal Adhesion ◽  
Early Embryogenesis ◽  
Actin Dynamics ◽  
Convergent Extension ◽  
Cortical Actin ◽  
Functional Interaction ◽  
Cell Movements ◽  
Cellular Pathways ◽  
Antisense Morpholino ◽  
Subthreshold Level

Focal adhesion kinase (FAK) mediates vital cellular pathways during development. Despite its necessity, how FAK regulates and integrates with other signals during early embryogenesis remains poorly understood. We found that the loss of Fak1a impaired epiboly, convergent extension and hypoblast cell migration in zebrafish embryos. We also observed a clear disturbance in cortical actin at the blastoderm margin and distribution of yolk syncytial nuclei. In addition, we investigated a possible link between Fak1a and a well-known gastrulation regulator, Wnt5b, and revealed that the overexpression of fak1a or wnt5b could cross-rescue convergence defects induced by a wnt5b or fak1a antisense morpholino (MO), respectively. Wnt5b and Fak1a were shown to converge in regulating Rac1 and Cdc42, which could synergistically rescue wnt5b and fak1a morphant phenotypes. Furthermore, we generated several alleles of fak1a mutants using CRISPR/Cas9, but those mutants only revealed mild gastrulation defects. However, injection of a subthreshold level of the wnt5b MO induced severe gastrulation defects in fak1a mutants, which suggested that the upregulated expression of wnt5b might complement the loss of Fak1a. Collectively, we demonstrated that a functional interaction between Wnt and FAK signalling mediates gastrulation cell movements via the possible regulation of Rac1 and Cdc42 and subsequent actin dynamics.

scholarly journals The Cytoskeleton-associated PDZ-LIM Protein, ALP, Acts on Serum Response Factor Activity to Regulate Muscle Differentiation

2007 ◽  
Vol 18 (5) ◽  
pp. 1723-1733 ◽  
Author(s):  
Pascal Pomiès ◽  
Mohammad Pashmforoush ◽  
Cristina Vegezzi ◽  
Kenneth R. Chien ◽  
Charles Auffray ◽  
...  
Keyword(s):  
Serum Response Factor ◽  
Critical Role ◽  
Muscle Differentiation ◽  
Actin Dynamics ◽  
Response Factor ◽  
Cytoskeletal Regulation ◽  
Expression Construct ◽  
Filament Bundles ◽  
Serum Response

In this report, an antisense RNA strategy has allowed us to show that disruption of ALP expression affects the expression of the muscle transcription factors myogenin and MyoD, resulting in the inhibition of muscle differentiation. Introduction of a MyoD expression construct into ALP-antisense cells is sufficient to restore the capacity of the cells to differentiate, illustrating that ALP function occurs upstream of MyoD. It is known that MyoD is under the control of serum response factor (SRF), a transcriptional regulator whose activity is modulated by actin dynamics. A dramatic reduction of actin filament bundles is observed in ALP-antisense cells and treatment of these cells with the actin-stabilizing drug jasplakinolide stimulates SRF activity and restores the capacity of the cells to differentiate. Furthermore, we show that modulation of ALP expression influences SRF activity, the level of its coactivator, MAL, and muscle differentiation. Collectively, these results suggest a critical role of ALP on muscle differentiation, likely via cytoskeletal regulation of SRF.

scholarly journals Coronin 1A depletion restores the nuclear stability and viability of Aip1/Wdr1-deficient neutrophils

2019 ◽  
Vol 218 (10) ◽  
pp. 3258-3271
Author(s):  
Charnese Bowes ◽  
Michael Redd ◽  
Malika Yousfi ◽  
Muriel Tauzin ◽  
Emi Murayama ◽  
...  
Keyword(s):  
Cell Death ◽  
Actin Filaments ◽  
Essential Role ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Zebrafish Embryos ◽  
Actomyosin Contractility ◽  
Nuclear Stability

Actin dynamics is central for cells, and especially for the fast-moving leukocytes. The severing of actin filaments is mainly achieved by cofilin, assisted by Aip1/Wdr1 and coronins. We found that in Wdr1-deficient zebrafish embryos, neutrophils display F-actin cytoplasmic aggregates and a complete spatial uncoupling of phospho-myosin from F-actin. They then undergo an unprecedented gradual disorganization of their nucleus followed by eruptive cell death. Their cofilin is mostly unphosphorylated and associated with F-actin, thus likely outcompeting myosin for F-actin binding. Myosin inhibition reproduces in WT embryos the nuclear instability and eruptive death of neutrophils seen in Wdr1-deficient embryos. Strikingly, depletion of the main coronin of leukocytes, coronin 1A, fully restores the cortical location of F-actin, nuclear integrity, viability, and mobility of Wdr1-deficient neutrophils in vivo. Our study points to an essential role of actomyosin contractility in maintaining the integrity of the nucleus of neutrophils and a new twist in the interplay of cofilin, Wdr1, and coronin in regulating F-actin dynamics.

scholarly journals Activity of Smurf2 Ubiquitin Ligase Is Regulated by the Wnt Pathway Protein Dishevelled

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1147 ◽  
Author(s):  
Ondrej Bernatik ◽  
Petra Paclikova ◽  
Ranjani Sri Ganji ◽  
Vitezslav Bryja
Keyword(s):  
Signaling Pathways ◽  
Ubiquitin Ligase ◽  
Planar Cell Polarity ◽  
Wnt Pathway ◽  
Bmp Signaling ◽  
Hek293 Cells ◽  
Convergent Extension ◽  
Organ Systems ◽  
Pcp Signaling

Wnt and BMP signaling pathways are two key molecular machineries regulating development and homeostasis. The efficient coordination of Wnt and BMP is essential in many developmental processes such as establishment of antero-posterior and dorso-ventral body axis, regulation of convergent extension, or development of various organ systems. SMAD ubiquitination regulatory factor (Smurf) family of E3 ubiquitin ligases are important and evolutionary conserved regulators of TGF-β/BMP signaling pathways. Smurf2 has been previously shown to regulate Wnt/planar cell polarity (PCP) signaling pathway by ubiquitinating Prickle1, one of the key components of PCP. We explored the role of Smurf2 in Wnt pathways in further detail and identified that Smurf2 is also a ubiquitin ligase of Dishevelled (DVL), the key cytoplasmic signal transducer in the Wnt pathway. Interestingly, the Smurf2 and DVL relationship expands beyond substrate-E3 ligase. We can show that DVL activates Smurf2, which allows Smurf2 to ubiquitinate its substrates from Wnt/PCP (Prickle1) as well as TGF-β/BMP (Smad2) pathways more efficiently. Using SMAD7 as an example of Smurf2 activator we show that DVL and SMAD7 both activates Smurf2 activity. In HEK293 cells the deficiency of DVL phenocopies absence of Smurf2 and leads to the increased phosphorylation of R-Smads. Smurf2-DVL connection provides a novel and intriguing point of crosstalk for Wnt and BMP pathways.

Actin dynamics as critical ion channel regulator: ENaC and Piezo in focus

2021 ◽  
Author(s):  
Elena A. Morachevskaya ◽  
Anastasia V. Sudarikova
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Dynamic Balance ◽  
Cell Volume Regulation ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Actin Assembly ◽  
Excitable Cells ◽  
Physiological Processes

Ion channels in plasma membrane play a principal role in different physiological processes, including cell volume regulation, signal transduction and modulation of membrane potential in living cells. Actin-based cytoskeleton, which exists in a dynamic balance between monomeric and polymeric forms (globular and fibrillar actin), can be directly or indirectly involved in various cellular responses including modulation of ion channel activity. In this mini-review, we present an overview of the role of submembranous actin dynamics in the regulation of ion channels in excitable and non-excitable cells. Special attention is focused on the important data about the involvement of actin assembly/disassembly and some actin-binding proteins in the control of the Epithelial Na+ Channel (ENaC) and mechanosensitive Piezo channels whose integral activity has potential impact on membrane transport and multiple coupled cellular reactions. Growing evidence suggests that actin elements of the cytoskeleton can represent a "converging point" of various signaling pathways modulating the activity of ion transport proteins in cell membranes.

Actinin-4 is preferentially involved in circular ruffling and macropinocytosis in mouse macrophages: analysis by fluorescence ratio imaging

2000 ◽  
Vol 113 (18) ◽  
pp. 3329-3340 ◽  
Author(s):  
N. Araki ◽  
T. Hatae ◽  
T. Yamada ◽  
S. Hirohashi
Keyword(s):  
Actin Dynamics ◽  
Actin Binding ◽  
Imaging Data ◽  
Fluorescence Ratio ◽  
Mouse Macrophages ◽  
Fluorescence Ratio Imaging ◽  
Different Types ◽  
Ratio Imaging ◽  
Reduced Rate

We have applied fluorescence ratio imaging to the analysis of an actin-binding protein concentration relative to F-actin in macrophages, in order to explore the role of a novel (alpha)-actinin isoform, actinin-4, relative to that of the classical isoform, actinin-1. Conventional immunofluorescence images showed that both isoforms were enriched in F-actin-rich regions such as cell surface ruffles. However, ratio images further demonstrated that actinin-4 concentrations relative to F-actin were higher in peripheral inward curved ruffles and dorsal circular ruffles, presumed precursor forms of macropinosomes, than in straight linear ruffles, while actinin-1 concentrations were uniform among the different types of ruffles. Macropinosome pulse-labeling and chase experiments indicated that actinin-4 was also closely associated with newly formed macropinosomes and gradually dissociated with their maturation. Consistent with ratio imaging data, macrophages scrape-loaded with anti-actinin-4 showed a more reduced rate of macropinocytosis than those loaded with anti-actinin-1. Altogether, these results indicate that actinin-4 and actinin-1 contribute differently to F-actin dynamics, that actinin-4 is more preferentially involved in early stages of macropinocytosis than actinin-1. A similar redistribution of actinin-4 was also observed during phagocytosis, suggesting that actinin-4 may play the same role in the two mechanistically analogous types of endocytosis, i.e. macropinocytosis and phagocytosis.

scholarly journals The Role of Actin Dynamics and Actin-Binding Proteins Expression in Epithelial-to-Mesenchymal Transition and Its Association with Cancer Progression and Evaluation of Possible Therapeutic Targets

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Magdalena Izdebska ◽  
Wioletta Zielińska ◽  
Dariusz Grzanka ◽  
Maciej Gagat
Keyword(s):  
Cancer Progression ◽  
Binding Proteins ◽  
Therapeutic Potential ◽  
Tumour Progression ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Site Formation ◽  
Actin Binding Proteins ◽  
Mesenchymal Transition

Metastasis causes death of 90% of cancer patients, so it is the most significant issue associated with cancer disease. Thus, it is no surprise that many researchers are trying to develop drugs targeting or preventing them. The secondary tumour site formation is closely related to phenomena like epithelial-to-mesenchymal and its reverse, mesenchymal-to-epithelial transition. The change of the cells’ phenotype to mesenchymal involves the acquisition of migratory potential. Cancer cells movement is possible due to the development of invasive structures like invadopodia, lamellipodia, and filopodia. These changes are dependent on the reorganization of the actin cytoskeleton. In turn, the polymerization and depolymerization of actin are controlled by actin-binding proteins. In many tumour cells, the actin and actin-associated proteins are accumulated in the cell nucleus, suggesting that it may also affect the progression of cancer by regulating gene expression. Once the cancer cell reaches a new habitat it again acquires epithelial features and thus proliferative activity. Targeting of epithelial-to-mesenchymal or/and mesenchymal-to-epithelial transitions through regulation of their main components expression may be a potential solution to the problem of metastasis. This work focuses on the role of these processes in tumour progression and the assessment of therapeutic potential of agents targeting them.

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