Contribution of Filopodia to Cell Migration: A Mechanical Link between Protrusion and Contraction

Numerous F-actin containing structures are involved in regulating protrusion of membrane at the leading edge of motile cells. We have investigated the structure and dynamics of filopodia as they relate to events at the leading edge and the function of the trailing actin networks. We have found that although filopodia contain parallel bundles of actin, they contain a surprisingly nonuniform spatial and temporal distribution of actin binding proteins. Along the length of the actin filaments in a single filopodium, the most distal portion contains primarily T-plastin, while the proximal portion is primarily bound by α-actinin and coronin. Some filopodia are stationary, but lateral filopodia move with respect to the leading edge. They appear to form a mechanical link between the actin polymerization network at the front of the cell and the myosin motor activity in the cell body. The direction of lateral filopodial movement is associated with the direction of cell migration. When lateral filopodia initiate from and move toward only one side of a cell, the cell will turn opposite to the direction of filopodial flow. Therefore, this filopodia-myosin II system allows actin polymerization driven protrusion forces and myosin II mediated contractile force to be mechanically coordinated.

• Publication year

  2010

• Venue

  International Journal of Cell Biology

• Publication date

  2010-07-06

• Fields of study

  Biology, Medicine, Engineering

• Identifiers
  DOI 10.1155/2010/507821PMID 20671957PMCID 2910478
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Filopodia

  2020cited by this paper
• Unravelling the structure of the lamellipodium

  2008cited by this paper
• Building the actin cytoskeleton: filopodia contribute to the construction of contractile bundles in the lamella

  2008cited by this paper
• Coronin 1B coordinates Arp2/3 complex and cofilin activities at the leading edge.

  2007cited by this paper
• Role of fascin in filopodial protrusion

  2006cited by this paper
• On the edge: modeling protrusion.

  2006cited by this paper
• Stress fibers are generated by two distinct actin assembly mechanisms in motile cells

  2006cited by this paper
• Spatiotemporal feedback between actomyosin and focal-adhesion systems optimizes rapid cell migration.

  2006cited by this paper
• Myosin II functions in actin-bundle turnover in neuronal growth cones

  2006cited by this paper
• The making of filopodia.

  2006cited by this paper
• Coronin-1 function is required for phagosome formation.

  2005cited by this paper
• Phosphorylation of Coronin 1B by Protein Kinase C Regulates Interaction with Arp2/3 and Cell Motility*

  2005cited by this paper
• The Arg non-receptor tyrosine kinase modifies F-actin structure.

  2005cited by this paper
• The comings and goings of actin: coupling protrusion and retraction in cell motility.

  2005cited by this paper
• The Rho family GTPase Rif induces filopodia through mDia2.

  2005influential reference
• Phosphatidylinositol-4,5-bisphosphate hydrolysis directs actin remodeling during phagocytosis

  2005cited by this paper
• The Diaphanous-related formin dDia2 is required for the formation and maintenance of filopodia

  2005influential reference
• Lamellipodial versus filopodial mode of the actin nanomachinery: pivotal role of the filament barbed end.

  2004influential reference
• Alpha-actinin revisited: a fresh look at an old player.

  2004cited by this paper
• Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein

  2004cited by this paper
• Mechanism of filopodia initiation by reorganization of a dendritic network

  2003influential reference
• Disruption of the Diaphanous-related formin Drf1 gene encoding mDia1 reveals a role for Drf3 as an effector for Cdc42.

  2003influential reference
• Cellular motility driven by assembly and disassembly of actin filaments.

  2003cited by this paper
• Two-piconewton slip bond between fibronectin and the cytoskeleton depends on talin

  2003cited by this paper
• Cofilin produces newly polymerized actin filaments that are preferred for dendritic nucleation by the Arp2/3 complex.

  2002cited by this paper
• The lamellipodium: where motility begins.

  2002cited by this paper
• Rho-kinase and myosin-II control phagocytic cup formation during CR, but not FcgammaR, phagocytosis.

  2002cited by this paper
• Fascins, and their roles in cell structure and function.

  2002cited by this paper
• Structures in focus--filopodia.

  2002cited by this paper
• Towards a complete atomic structure of spectrin family proteins.

  2002cited by this paper
• Dictyostelium: Cell Motility and the Cytoskeleton

  2001cited by this paper
• Filopodia.

  2001cited by this paper
• Dynamics of alpha-actinin in focal adhesions and stress fibers visualized with alpha-actinin-green fluorescent protein.

  2001cited by this paper
• Dynamics of α‐actinin in focal adhesions and stress fibers visualized with α‐actinin‐green fluorescent protein

  2001cited by this paper
• Red fluorescent protein

  2001cited by this paper
• Mechanism of lateral movement of filopodia and radial actin bundles across neuronal growth cones.

  2000cited by this paper
• F-Actin Bundles Are Derivatives of Microvilli

  2000cited by this paper
• Parallel actin bundles and their multiple actin-bundling proteins.

  2000cited by this paper
• Conditional expression of a truncated fragment of nonmuscle myosin II-A alters cell shape but not cytokinesis in HeLa cells.

  2000cited by this paper
• Arp2/3 Complex and Actin Depolymerizing Factor/Cofilin in Dendritic Organization and Treadmilling of Actin Filament Array in Lamellipodia

  1999cited by this paper
• Rho GTPases and the actin cytoskeleton.

  1998influential reference
• Zyxin: Zinc fingers at sites of cell adhesion

  1997cited by this paper
• Cofilin Changes the Twist of F-Actin: Implications for Actin Filament Dynamics and Cellular Function

  1997cited by this paper
• Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness

  1997cited by this paper
• Analysis of the Actin–Myosin II System in Fish Epidermal Keratocytes: Mechanism of Cell Body Translocation

  1997cited by this paper
• Modulation of cell migration by integrin-mediated cytoskeletal linkages and ligand-binding affinity

  1996cited by this paper
• Cell motility driven by actin polymerization.

  1996cited by this paper
• Cell migration: a physically integrated molecular process.

  1996cited by this paper
• Paxillin association in vitro with integrin cytoplasmic domain peptides

  1996cited by this paper
• Myosin II filament assemblies in the active lamella of fibroblasts: their morphogenesis and role in the formation of actin filament bundles

  1995cited by this paper
• F-actin binding site masked by the intramolecular association of vinculin head and tail domains

  1995cited by this paper
• Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia.

  1995cited by this paper
• Dictyostelium mutants lacking the cytoskeletal protein coronin are defective in cytokinesis and cell motility

  1993cited by this paper
• Maximal migration of human smooth muscle cells on fibronectin and type IV collagen occurs at an intermediate attachment strength

  1993cited by this paper
• Actin filaments, stereocilia, and hair cells: how cells count and measure.

  1992cited by this paper
• Paxillin: a new vinculin-binding protein present in focal adhesions

  1990cited by this paper
• Microfilament-based motility in non-muscle cells.

  1989cited by this paper
• Cold Spring Harbor Symposia on Quantitative Biology.: Vol. LII. Evolution of Catalytic Functions. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 1987, ISBN 0-87969-054-2, xix + 955 pp., US $150.00.

  1989cited by this paper
• Preliminary biochemical characterization of the stereocilia and cuticular plate of hair cells of the chick cochlea

  1989cited by this paper
• Actin filaments, stereocilia, and hair cells of the bird cochlea. V. How the staircase pattern of stereociliary lengths is generated

  1988cited by this paper
• Behaviour and structure of the leading lamella in moving fibroblasts. I. Occurrence and centripetal movement of arc-shaped microfilament bundles beneath the dorsal cell surface.

  1983cited by this paper
• Actin filaments, stereocilia, and hair cells of the bird cochlea. II. Packing of actin filaments in the stereocilia and in the cuticular plate and what happens to the organization when the stereocilia are bent

  1983cited by this paper
• Cytostructural dynamics of spreading and translocating cells

  1982cited by this paper
• How actin filaments pack into bundles.

  1982cited by this paper

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  2025cites this paper
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  2025cites this paper
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  2025cites this paper
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  2023cites this paper
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  2022cites this paper
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  2022cites this paper
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  2022cites this paper
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  2022cites this paper
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  2022cites this paper
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  2021influential citation
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