Disease relevance of Pseudopodia

• To propel itself in infected cells, the pathogen Shigella flexneri subverts the Cdc42-controlled machinery responsible for actin assembly during filopodia formation [1].
• RalA does not generate filopodia in filamin-deficient human melanoma cells, whereas transfection of filamin 1 restores the functional response [2].
• Here we show that microinjection of Cdc42Hs and Rac1 promoted formation of filopodia and lamellipodia in N1E-115 neuroblastoma growth cones and along neurites [3].
• Increased beta-actin expression in an invasive moloney sarcoma virus-transformed MDCK cell variant concentrates to the tips of multiple pseudopodia [4].
• Accordingly, primary human schwannoma cells lacking merlin show an increased number of lamellipodia and filopodia as well as increased cell spreading [5].

High impact information on Pseudopodia

• In Ena/VASP deficient cells, CP depletion resulted in ruffling instead of filopodia [6].
• In spreading and migrating cells we find local periodic contractions of lamellipodia that depend on matrix rigidity, fibronectin binding and myosin light chain kinase (MLCK) [7].
• Taken together, a dynamic mechanism for intercellular adhesion is unveiled involving calcium-activated filopodia penetration and VASP/Mena-dependent actin reorganization/polymerization [8].
• E-cadherin complexes cluster at filopodia tips, generating a two-rowed zipper of embedded puncta [8].
• Rac and Cdc42 regulate a variety of responses in mammalian cells including formation of lamellipodia and filopodia, activation of the JNK MAP kinase cascade, and induction of G1 cell cycle progression [9].

Chemical compound and disease context of Pseudopodia

• Polystyrene microspheres and synthetic phospholipid vesicles coated with proteins that initiate actin polymerization display motile behavior similar to Listeria, mimicking the leading edge of lamellipodia and filopodia [10].
• Ethyl palmitate induces abnormal movement and the formation of unusual club shaped pseudopodia; ethyl palmitate prevents the ingestion of antibody coated erythrocytes and it is postulated that this substance interferes with the syntheses of IgG receptors [11].
• Pretreatment of the lymphoma cells with C3, in conditions where Rho was actually ADP-ribosylated, strongly inhibited the characteristic shape changes resulting from extension and retraction of pseudopodia [12].

Biological context of Pseudopodia

• Rearrangement of cytoplasm, fusion of membranous organelles with the plasma membrane and growth of pseudopodia, all characteristic of in vivo spermiogenesis, occur within five minutes after exposure to monensin at concentrations of 0.1-1.0 micronM [13].
• Consistent with a role in mediating matrix adhesion and migration ultrastructurally, CD44 was found uniformly over the cell surface and was found densely labeling filopodia and lamellipodia, highly motile structures involved in cell migration [14].
• Importantly, knock-down of Myo10 by short interfering RNA impaired integrin function in cell adhesion, whereas overexpression of Myo10 stimulated the formation and elongation of filopodia in an integrin-dependent manner and relocalized integrins together with Myo10 to the tips of filopodia [15].
• Treatment with Y-27632 or ML-7 that inhibits myosin phosphorylation and contractility increased lamellipodia through Rac activation and decreased cell polarization [16].
• Significantly, we establish that sustained TAM67 expression inhibits growth factor-induced cell motility and the reorganization of the cytoskeleton and cell-shape changes essential for this process: TAM67 expression inhibits EGF-induced membrane ruffling, lamellipodia formation, cortical actin polymerization and cell rounding [17].

Anatomical context of Pseudopodia

• Neuronal filopodia are actin-rich cytoplasmic extensions that are involved in motility and recognition in growth cones and maturing axonal endings [18].
• Integrin-mediated adhesion activates these GTPases, triggering assembly of filopodia, lamellipodia and stress fibers [19].
• In macrophages that have spread on the substratum, MARCKS has a punctate distribution at the cell-substratum interface of pseudopodia and filopodia [20].
• Mononuclear and PMN leukocytes accumulated in glomerular capillaries, adhered to the capillary wall, and extended pseudopodia through the endothelial fenestrae to contact in the LRI of the GBM where the immune deposits and C3 were located [21].
• Here, we show that fibroblast lamellipodia extend along held collagen fibres, bind, and retract them in a 'hand-over-hand' cycle, involving alpha2beta1 integrin [22].

Associations of Pseudopodia with chemical compounds

• Washed platelets activated by alpha-thrombin, gamma-thrombin, thrombocytin or the ionophore A23187 (ref. 3) lose their disk shape, produce pseudopodia and become cohesive [23].
• Consistent with this idea, we found opposing defects in embryos harboring only a heparin-binding isoform of VEGF-A, including excess endothelial filopodia and abnormally thin vessel branches in ectopic sites [24].
• These processes are associated with the extension of lamellipodia and require actin polymerization, tyrosine kinase activation, cytoplasmic calcium increases, and LAT, an important hematopoietic adaptor [25].
• Glutamate regulates actin-based motility in axonal filopodia [26].
• Activation of protein kinase C results in the displacement of its myristoylated, alanine-rich substrate from punctate structures in macrophage filopodia [20].

Gene context of Pseudopodia

• The mammalian Rac and Cdc42 proteins control formation of lamellipodia and filopodia, respectively [27].
• This integrin relocalization and filopodia elongation did not occur with Myo10 mutants deficient in integrin binding or with a beta(1)-integrin point mutant deficient in Myo10 binding [15].
• Rho-dependent stress fiber formation and Rho-dependent focal contact protein phosphorylation were also inhibited, whereas Cdc42 was activated, leading to actin polymerization into filopodia [28].
• The mechanisms through which the small GTPases Rac1 and Cdc42 regulate the formation of membrane ruffles, lamellipodia, and filopodia are currently unknown [29].
• VASP increases branch spacing of filaments in the actin tail, as it does in lamellipodia in living cells [30].

Analytical, diagnostic and therapeutic context of Pseudopodia

• Microinjection of WIP into NIH 3T3 fibroblasts induces filopodia; this is inhibited by microinjection of anti-N-WASP antibody [31].
• Anti-actin immunofluorescence and rhodamine phalloidin staining of f-actin both showed intense staining of filopodia and lamellipodia [32].
• Confocal microscopy analysis of endogenous PSTPIP revealed colocalization with the cortical actin cytoskeleton, lamellipodia, and actin-rich cytokinetic cleavage furrow [33].
• Indirect immunofluorescence microscopy revealed that the alpha6beta4 integrin is localized as discrete clusters in filopodia, lamellae, and retraction fibers [34].
• Platelets isolated by centrifugation in the absence of prostacyclin were not discoid, but were instead irregular with one or more pseudopodia [35].

References