A sensory role for neuronal growth cone filopodia

Davenport, Roger W.; Dou, Ping; Rehder, Vincent; Kater, Stanley B.

doi:10.1038/361721a0

Cited by 203 publications

(124 citation statements)

References 33 publications

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“…Filopodia are finger-like plasma membrane protrusions that are formed upon remodelling of the actin cytoskeleton beneath the plasma membrane 13 . They can be viewed as a sensory organ of the cells that are used to detect and assimilate signals as well as to explore and move into the surrounding microenvironment [14][15][16] . Filopodia are also involved in transporting signalling proteins within tissues over a long range 16 .…”

mentioning

confidence: 99%

Targeted inhibition of fascin function blocks tumour invasion and metastatic colonization

et al. 2015

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One of the key steps during tumour metastasis is tumour cell migration and invasion, which require actin cytoskeletal reorganization. Among the critical actin cytoskeletal protrusion structures are the filopodia, which act like cell sensory organs to communicate with the extracellular microenvironment and participate in fundamental cell functions such as cell adhesion, spreading and migration in the three-dimensional environment. Fascin is the main actin-bundling protein in filopodia. Using high-throughput screening, here we identify and characterize small molecules that inhibit the actin-bundling activity of fascin. Focusing on one such inhibitor, we demonstrate that it specifically blocks filopodial formation, tumour cell migration and invasion in vitro, and metastasis in vivo. Hence, target-specific anti-fascin agents have a therapeutic potential for cancer treatment.

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confidence: 99%

Targeted inhibition of fascin function blocks tumour invasion and metastatic colonization

et al. 2015

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“…Indeed, the interplay between lamellipodia and filopodia during cell spreading and motility is still controversial. The classical view is that the primary function of filopodia is to sample the immediate environment and to transduce signals that trigger the extension of lamellipodia in a distinct process [14] and [15]. The choice between one and the other mode in actin polymerization would be dependent on the capping protein at the barbed end [16].…”

Section: Introductionmentioning

confidence: 99%

Lamellipodia nucleation by filopodia depends on integrin occupancy and downstream Rac1 signaling

Guillou

Depraz-Depland

Planus

et al. 2008

Experimental Cell Research

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Time-lapse video-microscopy unambiguously shows that fibroblast filopodia are the scaffold of lamellipodia nucleation that allows anisotropic cell spreading. This process was dissected into elementary stages by monitoring cell adhesion on micropatterned extracellular matrix arrays of various pitches. Adhesion structures are stabilized by contact with the adhesive plots and subsequently converted into lamellipodia-like extensions starting at the filopodia tips. This mechanism progressively leads to full cell spreading. Stable expression of the dominantnegative Rac1 N17 impairs this change in membrane extension mode and stops cell spreading on matrix arrays. Similar expression of the dominant-negative Cdc42 N17 impairs cell spreading on homogenous and structured substrate, suggesting that filopodia extension is a prerequisite for cell spreading in this model. The differential polarity of the nucleation of lamellipodial structures by filopodia on homogenous and structured surfaces starting from the cell body and of filopodia tip, respectively, suggested that this process is triggered by areas that are in contact with extracellular matrix proteins for longer times. Consistent with this view, wild-type cells cannot spread on microarrays made of function blocking or neutral anti-β 1 integrin antibodies. However, stable expression of a constitutively active Rac1 mutant rescues the cell ability to spread on these integrin microarrays. Thereby, lamellipodia nucleation by filopodia requires integrin occupancy by matrix substrate and downstream Rac1 signaling.

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“…Soluble ligands also can cause collapse (Pini, 1993). Since serotonin, a G protein-coupled receptor, exerts this function in other organisms (Haydon et al, 1984;Davenport et al, 1993) and DRG bear 5-HT receptors (Todorovic and Anderson, 1990), we have examined 5-HT as a defined soluble ligand, and found it causes growth cone collapse, which is blocked by 5-HT, receptors. Thus, our interpretation is that GAP-43 serves to amplify a variety of guidance signals from growth cones.…”

Section: G and Growth Cone Collapsementioning

confidence: 99%

“…Peptides augment 5-HT-induced collapse Soluble factors, including neurotransmitters (Davenport et al, 1993), have been identified as important in directing (Kennedy et al, 1994) and retarding neuronal growth (Pini, 1993). In other species, serotonin (5-HT) causes growth cone collapse (Haydon et al, 1984) and downregulation of NCAM-like molecules and fasciculation (Peter et al, 1994).…”

Section: Intracellular Injection Of Peptidesmentioning

confidence: 99%

Ligand-induced growth cone collapse: amplification and blockade by variant GAP-43 peptides

Igarashi

Sudo

et al. 1995

J. Neurosci.

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Growth cones are powerful amplifiers for signals from the microenvironment. Their collapse can be triggered by cell surface components of myelin and brain membranes, as well as by soluble ligands, including neurotransmitters. GAP-43 is a protein concentrated on the inner surface of the growth cone membrane. Assayed in isolation, it interacts with the heterotrimeric protein, G(o), and in oocytes it amplifies the effects of ligand-triggered G protein activation. We wished to examine whether GAP-43 serves to amplify signals at the growth cone. The G(o) stimulating region of GAP-43 is encoded in the 10 amino acids (MLCCMRRT-KQ) of the first exon. We examined the effect of this peptide upon chick dorsal root ganglion growth cone collapse and neurite retraction triggered by brain membranes or myelin, as well as by serotonin. We find that application of the GAP-43 1–10 peptide amplifies the effects of all three ligands. The amplification is greater when GAP-43 1–10 is injected intracellularly. Peptides with amino acid substitutions for the two cysteine residues manifest parallel changes in growth cone collapse and G(o) stimulation. In particular, tyrosine or methionine substitutions cause the peptide to inhibit G(o) and to block induced growth cone collapse. The GAP-43 peptides therefore regulate the sensitivity of growth cones to extrinsic signals. The modified peptides serve as a starting point for the design of reagents to enhance CNS regeneration.

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A sensory role for neuronal growth cone filopodia

Cited by 203 publications

References 33 publications

Targeted inhibition of fascin function blocks tumour invasion and metastatic colonization

Targeted inhibition of fascin function blocks tumour invasion and metastatic colonization

Lamellipodia nucleation by filopodia depends on integrin occupancy and downstream Rac1 signaling

Ligand-induced growth cone collapse: amplification and blockade by variant GAP-43 peptides

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