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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 -
Journal of Cell Science Mar 2023Myosin-X (MYO10), a molecular motor localizing to filopodia, is thought to transport various cargo to filopodia tips, modulating filopodia function. However, only a few...
Myosin-X (MYO10), a molecular motor localizing to filopodia, is thought to transport various cargo to filopodia tips, modulating filopodia function. However, only a few MYO10 cargoes have been described. Here, using GFP-Trap and BioID approaches combined with mass spectrometry, we identified lamellipodin (RAPH1) as a novel MYO10 cargo. We report that the FERM domain of MYO10 is required for RAPH1 localization and accumulation at filopodia tips. Previous studies have mapped the RAPH1 interaction domain for adhesome components to its talin-binding and Ras-association domains. Surprisingly, we find that the RAPH1 MYO10-binding site is not within these domains. Instead, it comprises a conserved helix located just after the RAPH1 pleckstrin homology domain with previously unknown functions. Functionally, RAPH1 supports MYO10 filopodia formation and stability but is not required to activate integrins at filopodia tips. Taken together, our data indicate a feed-forward mechanism whereby MYO10 filopodia are positively regulated by MYO10-mediated transport of RAPH1 to the filopodium tip.
Topics: Pseudopodia; Binding Sites; Integrins; Mass Spectrometry; Myosins
PubMed: 36861887
DOI: 10.1242/jcs.260574 -
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 -
Current Opinion in Cell Biology Feb 2006Filopodia are rod-like cell surface projections filled with bundles of parallel actin filaments. They are found on a variety of cell types and have been ascribed sensory... (Review)
Review
Filopodia are rod-like cell surface projections filled with bundles of parallel actin filaments. They are found on a variety of cell types and have been ascribed sensory or exploratory functions. Filopodium formation is frequently associated with protrusion of sheet-like actin filament arrays called lamellipodia and membrane ruffles, but, in comparison to these structures, the molecular details underpinning the initiation and maintenance of filopodia are only just beginning to emerge. Recent advances have improved our understanding of the molecular requirements for filopodium protrusion and have yielded insights into the inter-relationships between lamellipodia and filopodia, the two 'sub-compartments' of the protrusive actin cytoskeleton.
Topics: Animals; Dictyostelium; Mice; Microfilament Proteins; Models, Biological; Pseudopodia; Signal Transduction
PubMed: 16337369
DOI: 10.1016/j.ceb.2005.11.002 -
Seminars in Cell & Developmental Biology Jan 2023Brain development relies on dynamic morphogenesis and interactions of neurons. Filopodia are thin and highly dynamic membrane protrusions that are critically required... (Review)
Review
Brain development relies on dynamic morphogenesis and interactions of neurons. Filopodia are thin and highly dynamic membrane protrusions that are critically required for neuronal development and neuronal interactions with the environment. Filopodial interactions are typically characterized by non-deterministic dynamics, yet their involvement in developmental processes leads to stereotypic and robust outcomes. Here, we discuss recent advances in our understanding of how filopodial dynamics contribute to neuronal differentiation, migration, axonal and dendritic growth and synapse formation. Many of these advances are brought about by improved methods of live observation in intact developing brains. Recent findings integrate known and novel roles ranging from exploratory sensors and decision-making agents to pools for selection and mechanical functions. Different types of filopodial dynamics thereby reveal non-deterministic subcellular decision-making processes as part of genetically encoded brain development.
Topics: Pseudopodia; Neurogenesis; Neurons; Morphogenesis; Brain
PubMed: 35397971
DOI: 10.1016/j.semcdb.2022.03.038 -
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 Biology : CB Aug 2001
Topics: Actins; Animals; Cell Movement; Cytoskeleton; Pseudopodia; Sea Urchins
PubMed: 11525752
DOI: 10.1016/s0960-9822(01)00378-5 -
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 -
Trends in Cell Biology Jun 2014Long-distance cell-cell communication is essential for organ development and function. Whereas neurons communicate at long distances by transferring signals at sites of... (Review)
Review
Long-distance cell-cell communication is essential for organ development and function. Whereas neurons communicate at long distances by transferring signals at sites of direct contact (i.e., at synapses), it has been presumed that the only way other cell types signal is by dispersing signals through extracellular fluid--indirectly. Recent evidence from Drosophila suggests that non-neuronal cells also exchange signaling proteins at sites of direct contact, even when long distances separate the cells. We review here contact-mediated signaling in neurons and discuss how this signaling mechanism is shared by other cell types.
Topics: Animals; Cell Communication; Drosophila; Humans; Neurons; Pseudopodia; Synapses
PubMed: 24560610
DOI: 10.1016/j.tcb.2014.01.003 -
Current Opinion in Cell Biology Oct 2015This review discusses recent advances in our understanding of the role filopodia and filopodia-like structures in cell adhesion and three dimensional (3D) cell migration... (Review)
Review
This review discusses recent advances in our understanding of the role filopodia and filopodia-like structures in cell adhesion and three dimensional (3D) cell migration both in vitro and in vivo. In particular, we focus on recent advances demonstrating that filopodia are involved in substrate tethering and environment sensing in vivo. We further discuss the emerging role of filopodia and filopodial proteins in tumor dissemination as mounting in vitro, in vivo and clinical evidence suggest that filopodia drive cancer cell invasion and highlight filopodia proteins as attractive therapeutic targets. Finally, we outline outstanding questions that remain to be addressed to elucidate the role of filopodia during 3D cell migration.
Topics: Animals; Cell Adhesion; Cell Movement; Humans; Neoplasm Invasiveness; Neoplasms; Pseudopodia
PubMed: 26186729
DOI: 10.1016/j.ceb.2015.06.007