Formation of filopodia in coelomocytes: Localization of Fascin, a 58,000 Dalton actin cross-linking protein

Otto, Joann J.; Kane, Robert E.; Bryan, Joseph

doi:10.1016/0092-8674(79)90154-5

Cited by 160 publications

(116 citation statements)

References 9 publications

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“…Fascin-1 is expressed in most mammalian tissues, with higher levels of expression in the brain, lung and testis. It binds actin at a stoichiometry of 1:4 and bundles F-actin in vitro (Bryan, 1986;Otto et al, 1979;1980). Fascin-2 is expressed in the photoreceptors of bovine and human retina (Tubb et al, 2000), and may function in the lamellipodial extension of new photoreceptor disks.…”

Section: Resultsmentioning

confidence: 99%

Neurotrophin-induced melanoma cell migration is mediated through the actin-bundling protein fascin

et al. 2003

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Expression of the p75 neurotrophin receptor (p75 NTR ) in primary melanomas is associated with deeply invasive lesions. In turn, there is expression of high levels of neurotrophins at the invasion front of normal tissue adjacent to brain metastases, thus implicating this growth factor-receptor system in melanoma tumorigenesis. The neurotrophins nerve growth factor (NGF) and neurotrophin-3 (NT-3) are potent chemotactic agents for human melanoma cells which express p75 NTR in vitro. Here we show that the actin-bundling protein fascin specifically interacts with p75 NTR in an NGF-dependent manner by coimmunoprecipitation and colocalization in melanoma cells that express the two proteins endogenously. In addition, expression of a fascin point mutant at the serine phosphorylation site (serine 39) regulating actin binding abrogates neurotrophin-induced migration. These results suggest a causal role for NGF-mediated dephosphorylation of serine 39 on fascin in mediating actin binding and subsequent melanoma cell migration.

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Section: Resultsmentioning

confidence: 99%

Neurotrophin-induced melanoma cell migration is mediated through the actin-bundling protein fascin

et al. 2003

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“…Discrete bundles of actin filaments have been found in the intestinal brush border microvilli (4,25), the stereocilia of the inner ear (11,40), acrosomal processes of invertebrate sperm (39), filopodia of sea urchin coelomocytes (9), and in cytoplasmic processes of cultured mammalian cells (21). Actin filament bundles in intestinal microvilli and in coelomocytes form in conjunction with specific actin-binding proteins (4,5,24,26).…”

Section: Discussionmentioning

confidence: 99%

Microtubule-associated proteins (MAPs) and the organization of actin filaments in vitro.

Sattilaro¹,

Dentler²,

LeCluyse³

1981

The Journal of Cell Biology

166

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When purified muscle actin was mixed with microtubule-associated proteins (MAPs) prepared from brain microtubules assembled in vitro, actin filaments were organized into discrete bundles, 26 nm in diameter . MAP-2 was the principal protein necessary for the formation of the bundles. Analysis of MAP-actin bundle formation by sedimentation and electrophoresis revealed the bundles to be composed of^'20% MAP-2 and 80% actin by weight . Transverse striations were observed to occur at 28-nm intervals along negatively stained MAPactin bundles, and short projections,^'12 nm long and spaced at 28-nm intervals, were resolved by high-resolution metal shadowing. The formation of MAP-actin bundles was inhibited by millimolar concentrations of ATP, AMP-PCP (,ß,y-methylene-adenosine triphosphate), and pyrophosphate but not by AMP, ADP, or GTP. The addition of ATP to a solution containing MAP-actin bundles resulted in the dissociation of the bundles into individual actin filaments; discrete particles, presumably MAP-2, were periodically attached along the splayed filaments. These results demonstrate that MAPS can bind to actin filaments and can induce the reversible formation of actin filament bundles in vitro.During the past decade, increasing evidence has indicated that there is a cytoskeleton within the cytoplasm ofmost eucaryotic cells and that the movements of cells and of organelles within cells occur in association with the cytoskeleton . Although the protein composition ofthe cytoskeleton is not well understood, the best evidence suggests that the major cytoskeletal structures include actin filaments, microtubules, and "intermediate filaments" (22,27). If cytoplasmic movements occur in association with the cytoskeletal structures, then it is likely that the structures interact with one another to mediate the movements. For example, the apparent presence of actin, microtubules, and myosin in the mitotic apparatus (6,12,13,28,33) suggests that these structures may interact with one another to move the chromosomes. Axoplasmic transport may also require associations between microtubules, actin, intermediate filaments, or membrane vesicles (1,3,20,23,35) .Although it is tempting to speculate that associations between cytoskeletal structures are responsible for cell movements, there is little direct biochemical evidence to illustrate how these interactions may occur . Griffith and Pollard (15) recently presented viscometric and ultrastructural evidence for the interaction of actin filaments with microtubules, in addition to viscometric evidence of the interaction of actin with micro-THE JOURNAL OF CELL BIOLOGY " VOLUME 90 AUGUST 1981 467-473 ©The Rockefeller University Press " 0021-9525/81/08/0467/07 $1 .00 tubule-associated proteins (MAPs). Moreover, the associations were reversible upon the addition ofATP, ITP, pyrophosphate, and, to a lesser extent, other nucleotides .In this report, we present evidence that MAPs, in particular MAP-2, can reversibly induce the assembly of actin into discrete bundles offilaments co...

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“…Fascin is the primary actin cross-linker in filopodia and has no amino-acid sequence homology with other actin-binding proteins [20][21][22][23][24][25] . It has a molecular mass of B55 kDa, functions as a monomer and is required to maximally cross-link the actin filaments into straight, compact and rigid bundles, to impart distinct mechanical stiffness to actin bundles 26,27 .…”

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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Formation of filopodia in coelomocytes: Localization of Fascin, a 58,000 Dalton actin cross-linking protein

Cited by 160 publications

References 9 publications

Neurotrophin-induced melanoma cell migration is mediated through the actin-bundling protein fascin

Neurotrophin-induced melanoma cell migration is mediated through the actin-bundling protein fascin

Microtubule-associated proteins (MAPs) and the organization of actin filaments in vitro.

Targeted inhibition of fascin function blocks tumour invasion and metastatic colonization

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