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The Journal of Cell Biology Jun 2003Vascular endothelial growth factor (VEGF-A) is a major regulator of blood vessel formation and function. It controls several processes in endothelial cells, such as...
Vascular endothelial growth factor (VEGF-A) is a major regulator of blood vessel formation and function. It controls several processes in endothelial cells, such as proliferation, survival, and migration, but it is not known how these are coordinately regulated to result in more complex morphogenetic events, such as tubular sprouting, fusion, and network formation. We show here that VEGF-A controls angiogenic sprouting in the early postnatal retina by guiding filopodial extension from specialized endothelial cells situated at the tips of the vascular sprouts. The tip cells respond to VEGF-A only by guided migration; the proliferative response to VEGF-A occurs in the sprout stalks. These two cellular responses are both mediated by agonistic activity of VEGF-A on VEGF receptor 2. Whereas tip cell migration depends on a gradient of VEGF-A, proliferation is regulated by its concentration. Thus, vessel patterning during retinal angiogenesis depends on the balance between two different qualities of the extracellular VEGF-A distribution, which regulate distinct cellular responses in defined populations of endothelial cells.
Topics: Animals; Animals, Newborn; Astrocytes; Cell Differentiation; Cell Division; Cells, Cultured; Dose-Response Relationship, Drug; Endothelial Growth Factors; Endothelium, Vascular; Mice; Mice, Knockout; Neovascularization, Physiologic; Organ Culture Techniques; Pseudopodia; Retina; Retinal Artery; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2
PubMed: 12810700
DOI: 10.1083/jcb.200302047 -
Cell Proliferation Mar 2021Cancer cell migration to secondary organs remains an essential cause of death among breast cancer (BrCa) patients. Cell motility mainly relies on actin dynamics. Our...
OBJECTIVES
Cancer cell migration to secondary organs remains an essential cause of death among breast cancer (BrCa) patients. Cell motility mainly relies on actin dynamics. Our previous reports verified that dishevelled-associated activator of morphogenesis 1 (Daam1) regulates invadopodia extension and BrCa cell motility. However, how Daam1 is involved in actin filament assembly and promotes pseudopodia formation in BrCa cells remains unclear.
MATERIALS AND METHODS
One hundred human BrCa samples were collected at Women's Hospital of Nanjing Medical University. Immunohistochemistry (IHC) was used to examine Daam1 and Fascin expression. Wound healing and Boyden chamber assays were used to explore cell migration and pseudopodia extension of BrCa cells. Co-IP/pull down and Western blotting were performed to study the physical interaction between Daam1 and Fascin. Immunofluorescence assays were performed to observe whether Daam1 and Fascin were colocalized and mediated actin filament assembly.
RESULTS
Fascin was upregulated in BrCa tissues compared with that in paracarcinoma tissues. The downregulation of Fascin caused a decline in pseudopodia formation and cell motility. Moreover, we found that Daam1 interacted with Fascin via formin homology (FH) domains, especially the FH2 domain. Immunofluorescence assays showed that Daam1 and Fascin partially colocalized to actin filaments, and the knockdown of Daam1 or Fascin failed to colocalize to short and curved actin filaments.
CONCLUSIONS
Daam1 specifically binds to Fascin via FH domains and cooperatively facilitates pseudopodia formation and cell migration by promoting actin filament assembly in BrCa.
Topics: Actin Cytoskeleton; Adaptor Proteins, Signal Transducing; Breast Neoplasms; Cell Movement; Formins; Humans; Pseudopodia; rho GTP-Binding Proteins
PubMed: 33458919
DOI: 10.1111/cpr.12994 -
Wiley Interdisciplinary Reviews.... 2014Filopodia are cellular protrusions that have been implicated in many types of mechanosensory activities. Morphogens are signaling proteins that regulate the patterned... (Review)
Review
Filopodia are cellular protrusions that have been implicated in many types of mechanosensory activities. Morphogens are signaling proteins that regulate the patterned development of embryos and tissues. Both have long histories that date to the beginnings of cell and developmental biology in the early 20th century, but recent findings tie specialized filopodia called cytonemes to morphogen movement and morphogen signaling. This review explores the conceptual and experimental background for a model of paracrine signaling in which the exchange of morphogens between cells is directed to sites where cytonemes directly link cells that produce morphogens to cells that receive and respond to them.
Topics: Animals; Diffusion; Humans; Imaginal Discs; Morphogenesis; Pseudopodia; Signal Transduction; Synapses
PubMed: 25186102
DOI: 10.1002/wdev.151 -
International Journal of Molecular... Feb 2023Phagocytosis is one of the most polarised of all cellular activities. Both the stimulus (the target for phagocytosis) and the response (its internalisation) are focussed... (Review)
Review
Phagocytosis is one of the most polarised of all cellular activities. Both the stimulus (the target for phagocytosis) and the response (its internalisation) are focussed at just one part of the cell. At the locus, and this locus alone, pseudopodia form a phagocytic cup around the particle, the cytoskeleton is rearranged, the plasma membrane is reorganised, and a new internal organelle, the phagosome, is formed. The effect of signals from the stimulus must, thus, both be complex and yet be restricted in space and time to enable an effective focussed response. While many aspects of phagocytosis are being uncovered, the mechanism for the restriction of signalling or the effects of signalling remains obscure. In this review, the details of the problem of restricting chemical intracellular signalling are presented, with a focus on diffusion into the cytosol and of signalling lipids along the plasma membrane. The possible ways in which simple diffusion is overcome so that the restriction of signalling and effective phagocytosis can be achieved are discussed in the light of recent advances in imaging, biophysics, and cell biochemistry which together are providing new insights into this area.
Topics: Phagocytosis; Phagosomes; Pseudopodia; Cytoskeleton; Cytosol
PubMed: 36769146
DOI: 10.3390/ijms24032825 -
Development (Cambridge, England) Feb 2014Development creates a vast array of forms and patterns with elegant economy, using a small vocabulary of pattern-generating proteins such as BMPs, FGFs and Hh in similar... (Review)
Review
Development creates a vast array of forms and patterns with elegant economy, using a small vocabulary of pattern-generating proteins such as BMPs, FGFs and Hh in similar ways in many different contexts. Despite much theoretical and experimental work, the signaling mechanisms that disperse these morphogen signaling proteins remain controversial. Here, we review the conceptual background and evidence that establishes a fundamental and essential role for cytonemes as specialized filopodia that transport signaling proteins between signaling cells. This evidence suggests that cytoneme-mediated signaling is a dispersal mechanism that delivers signaling proteins directly at sites of cell-cell contact.
Topics: Animals; Cell Communication; Cell Surface Extensions; Drosophila; Imaginal Discs; Intercellular Signaling Peptides and Proteins; Models, Biological; Morphogenesis; Protein Transport; Pseudopodia; Signal Transduction
PubMed: 24496611
DOI: 10.1242/dev.086223 -
Cells Dec 2021The lamellipodia and pseudopodia of migrating cells are produced and maintained by the Scar/WAVE complex. Thus, actin-based cell migration is largely controlled through...
The lamellipodia and pseudopodia of migrating cells are produced and maintained by the Scar/WAVE complex. Thus, actin-based cell migration is largely controlled through regulation of Scar/WAVE. Here, we report that the Abi subunit-but not Scar-is phosphorylated in response to extracellular signalling in cells. Like Scar, Abi is phosphorylated after the complex has been activated, implying that Abi phosphorylation modulates pseudopodia, rather than causing new ones to be made. Consistent with this, Scar complex mutants that cannot bind Rac are also not phosphorylated. Several environmental cues also affect Abi phosphorylation-cell-substrate adhesion promotes it and increased extracellular osmolarity diminishes it. Both unphosphorylatable and phosphomimetic Abi efficiently rescue the chemotaxis of Abi KO cells and pseudopodia formation, confirming that Abi phosphorylation is not required for activation or inactivation of the Scar/WAVE complex. However, pseudopodia and Scar patches in the cells with unphosphorylatable Abi protrude for longer, altering pseudopod dynamics and cell speed. , in which Scar and Abi are both unphosphorylatable, can still form pseudopods, but migrate substantially faster. We conclude that extracellular signals and environmental responses modulate cell migration by tuning the behaviour of the Scar/WAVE complex after it has been activated.
Topics: Cell Adhesion; Cell Movement; Chemotactic Factors; Dictyostelium; Extracellular Space; Mutation; Osmotic Pressure; Phosphorylation; Protozoan Proteins; Pseudopodia; Signal Transduction; Wiskott-Aldrich Syndrome Protein Family
PubMed: 34943993
DOI: 10.3390/cells10123485 -
The Journal of Biological Chemistry Apr 2003Nonmotile cells extend and retract pseudopodia-like structures in a random manner, whereas motile cells establish a single dominant pseudopodium in the direction of...
Nonmotile cells extend and retract pseudopodia-like structures in a random manner, whereas motile cells establish a single dominant pseudopodium in the direction of movement. This is a critical step necessary for cell migration and occurs prior to cell body translocation, yet little is known about how this process is regulated. Here we show that myosin II light chain (MLC) phosphorylation at its regulatory serine 19 is elevated in growing and retracting pseudopodia. MLC phosphorylation in the extending pseudopodium was associated with strong and persistent amplification of extracellular-regulated signal kinase (ERK) and MLC kinase activity, which specifically localized to the leading pseudopodium. Interestingly, inhibition of ERK or MLC kinase activity prevented MLC phosphorylation and pseudopodia extension but not retraction. In contrast, inhibition of RhoA activity specifically decreased pseudopodia retraction but not extension. Importantly, inhibition of RhoA activity specifically blocked MLC phosphorylation associated with retracting pseudopodia. Inhibition of either ERK or RhoA signals prevents chemotaxis, indicating that both pathways contribute to the establishment of cell polarity and migration. Together, these findings demonstrate that ERK and RhoA are distinct pathways that control pseudopodia extension and retraction, respectively, through differential modulation of MLC phosphorylation and contractile processes.
Topics: 3T3 Cells; Animals; COS Cells; Cell Adhesion; Chemotaxis; Chlorocebus aethiops; Culture Media, Serum-Free; Enzyme Inhibitors; Extracellular Matrix; Flavonoids; Kinetics; Lysophospholipids; Mice; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Models, Biological; Pseudopodia; Recombinant Proteins; Transfection; rho GTP-Binding Proteins
PubMed: 12571246
DOI: 10.1074/jbc.M211873200 -
Current Opinion in Cell Biology Oct 2014Many eukaryotic cells regulate their polarity and motility in response to external chemical cues. While we know many of the linear connections that link receptors with... (Review)
Review
Many eukaryotic cells regulate their polarity and motility in response to external chemical cues. While we know many of the linear connections that link receptors with downstream actin polymerization events, we have a much murkier understanding of the higher order positive and negative feedback loops that organize these processes in space and time. Importantly, physical forces and actin polymerization events do not simply act downstream of chemotactic inputs but are rather involved in a web of reciprocal interactions with signaling components to generate self-organizing pseudopods and cell polarity. Here we focus on recent progress and open questions in the field, including the basic unit of actin organization, how cells regulate the number and speed of protrusions, and 2D versus 3D migration.
Topics: Actins; Animals; Cell Polarity; Chemotaxis; Eukaryotic Cells; Humans; Pseudopodia; Signal Transduction
PubMed: 24998184
DOI: 10.1016/j.ceb.2014.06.007 -
Current Opinion in Cell Biology Oct 2012Metastatic cancer cells produce invasive membrane protrusions called invadopodia and pseudopodia, which play a central role in driving cancer cell dissemination in the... (Review)
Review
Metastatic cancer cells produce invasive membrane protrusions called invadopodia and pseudopodia, which play a central role in driving cancer cell dissemination in the body. Malignant cells use these structures to attach to and degrade extracellular matrix proteins, generate force for cell locomotion, and to penetrate the vasculature. Recent work using unique subcellular fractionation methodologies combined with spatial genomic, proteomic, and phosphoproteomic profiling has provided insight into the invadopodiome and pseudopodiome signaling networks that control the protrusion of invasive membranes. Here I highlight how these powerful spatial 'omics' approaches reveal important signatures of metastatic cancer cells and possible new therapeutic targets aimed at treating metastatic disease.
Topics: Animals; Cell Movement; Extracellular Matrix; Gene Expression Regulation, Neoplastic; Humans; Molecular Targeted Therapy; Neoplasm Invasiveness; Neoplasms; Proteomics; Pseudopodia; RNA, Neoplasm
PubMed: 22980730
DOI: 10.1016/j.ceb.2012.08.005 -
Current Biology : CB Aug 2001
Topics: Actins; Animals; Cell Movement; Cytoskeleton; Pseudopodia; Sea Urchins
PubMed: 11525752
DOI: 10.1016/s0960-9822(01)00378-5