The Diaphanous-related formin dDia2 is required for the formation and maintenance of filopodia

Schirenbeck, A.; Bretschneider, Till; Arasada, Rajesh; Schleicher, Michael; Faix, Jan

doi:10.1038/ncb1266

Cited by 236 publications

(239 citation statements)

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“…In Dictyostelium cells, the Drf dDia2 was shown to be critical for filopodium formation suggesting that nucleation and/or elongation of filopodial actin filaments by a formin are key biochemical activities regulating the assembly of these structures (Figure 2) (Schirenbeck et al, 2005). Consistently, GFP-tagged dDia2 was shown to surf on distal tips of protruding filopodia (Schirenbeck et al, 2005).…”

Section: Forminssupporting

confidence: 48%

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Filopodia: Complex models for simple rods

Faix

Breitsprecher

Stradal

et al. 2009

The International Journal of Biochemistry & Cell Biology

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154

148

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CitationFilopodia: Complex models for simple rods., 41 (8- AbstractFilopodia are prominent cell surface protrusions filled with bundles of linear actin filaments that drive their protrusion. These structures are considered important sensory organelles, for instance in neuronal growth cones or during the fusion of sheets of epithelial tissues. In addition, they can serve a precursor function in adhesion site or stress fibre formation. Actin filament assembly is essential for filopodia formation and turnover, yet the precise molecular mechanisms of filament nucleation and/or elongation are controversial. Indeed, conflicting reports on the molecular requirements of filopodia initiation have prompted researchers to propose different types and/or alternative or redundant mechanisms mediating this process.However, recent data shed new light on these questions, and they indicate that the balance of a limited set of biochemical activities can determine the structural outcome of a given filopodium. Here we focus on discussing our current view of the relevance of these activities, and attempt to propose a molecular mechanism of filopodia assembly based on a single core machinery.2

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Section: Forminssupporting

confidence: 48%

“…Consistently, GFP-tagged dDia2 was shown to surf on distal tips of protruding filopodia (Schirenbeck et al, 2005). From the fifteen formin isoforms in mammalian cells, so far only two Drfs, referred to as mDia1/Drf1 and mDia2/Drf3, have been implicated in the assembly of filopodial actin filaments (Faix and Grosse, 2006).…”

Section: Forminsmentioning

confidence: 77%

Filopodia: Complex models for simple rods

Faix

Breitsprecher

Stradal

et al. 2009

The International Journal of Biochemistry & Cell Biology

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154

148

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“…Two major modes of nucleating new actin filaments exist: (i) the formin family of actin nucleators remain associated with the tip of growing filaments while new actin monomers are added. Concurrently, filaments are bundled through fascin cross-linking proteins [35], resulting in actin-cable like structures as observed in the loose matrix of the actin cortex, and also in fine cellular protrusions called filopodia, which contain about 10-30 parallel actin filaments. (ii) The Arp2/3 complex allows branching of new daughter filaments from existing filaments, and is primarily involved in nucleating dense networks associated with protruding pseudopodia [36].…”

Section: Plasticity Of the Actin System In Moving Cells: Creating Bunmentioning

confidence: 99%

Progress and perspectives in signal transduction, actin dynamics, and movement at the cell and tissue level: lessons fromDictyostelium

2016

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Movement of cells and tissues is a basic biological process that is used in development, wound repair, the immune response to bacterial invasion, tumour formation and metastasis, and the search for food and mates. While some cell movement is random, directed movement stimulated by extracellular signals is our focus here. This involves a sequence of steps in which cells first detect extracellular chemical and/or mechanical signals via membrane receptors that activate signal transduction cascades and produce intracellular signals. These intracellular signals control the motile machinery of the cell and thereby determine the spatial localization of the sites of force generation needed to produce directed motion. Understanding how force generation within cells and mechanical interactions with their surroundings, including other cells, are controlled in space and time to produce cell-level movement is a major challenge, and involves many issues that are amenable to mathematical modelling.

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“…Over 30 formins have been described to date, with more than 15 family members found in vertebrates (1). Formin activity is required in vivo for a diverse array of cellular functions, such as stress fiber formation, endosome motility, cell motility, cytokinetic ring formation, cell-cell junction assembly, filopodia formation, induction of cell polarity, and activation of the MAL/serum response factor signaling pathway (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). It is thought that at the core of all of these activities is the ability of formins to regulate actin cytoskeletal dynamics.…”

mentioning

confidence: 99%

Interaction of the N- and C-terminal Autoregulatory Domains of FRL2 Does Not Inhibit FRL2 Activity

Vaillant

Copeland

Davis

et al. 2008

Journal of Biological Chemistry

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Formin homology proteins are a highly conserved family of cytoskeletal remodeling proteins best known for their ability to induce the formation of long unbranched actin filaments. They accomplish this by nucleating the de novo polymerization of F-actin and also by acting as F-actin barbed end "leaky cappers" that allow filament elongation while antagonizing the function of capping proteins. More recently, it has been reported that the FH2 domains of FRL1 and mDia2 and the plant formin AFH1 are able to bind and bundle actin filaments via distinct mechanisms. We find that like FRL1, FRL2 and FRL3 are also able to bind and bundle actin filaments. In the case of FRL3, this activity is dependent upon a proximal DAD/WH2-like domain that is found C-terminal to the FH2 domain. In addition, we show that, like other Diaphanousrelated formins, FRL3 activity is subject to autoregulation mediated by the interaction between its N-terminal DID and C-terminal DAD. In contrast, the DID and DAD of FRL2 also interact in vivo and in vitro but without inhibiting FRL2 activity. These data suggest that current models describing DID/ DAD autoregulation via steric hindrance of FH2 activity must be revised. Finally, unlike other formins, we find that the FH2 and N-terminal dimerization domains of FRL2 and FRL3 are able to form hetero-oligomers.Formin homology proteins (formins) are a highly conserved family of cytoskeletal regulatory proteins. Over 30 formins have been described to date, with more than 15 family members found in vertebrates (1). Formin activity is required in vivo for a diverse array of cellular functions, such as stress fiber formation, endosome motility, cell motility, cytokinetic ring formation, cell-cell junction assembly, filopodia formation, induction of cell polarity, and activation of the MAL/serum response factor signaling pathway (2-13). It is thought that at the core of all of these activities is the ability of formins to regulate actin cytoskeletal dynamics. This is achieved through the activity of two conserved formin homology domains, FH1 and FH2. FH1 consists of proline-rich repeats of varying sizes that can serve as ligands for Src homology 3 and WW domains as well as the small actin-binding protein profilin (14,15). FH2 domains form a dimer that induces the polymerization of long, unbranched filaments. It does this by nucleating de novo actin polymerization and by associating with the F-actin barbed end as a "leaky capper," allowing filament elongation while antagonizing the function of capping proteins (16). However, not all formins nucleate or elongate F-actin with equal potency. For example, mDia1 is an extremely efficient nucleator of polymerization, and its association with the barbed end of actin filaments accelerates elongation (16,17). In contrast, the isolated FH2 domain of FHOD1 does not induce actin polymerization in vivo (18). In addition, FH2 activity may also be influenced by the activity of adjacent domains. For example, in INF2, a WH2 G-actin binding motif antagonizes the nucleation activ...

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The Diaphanous-related formin dDia2 is required for the formation and maintenance of filopodia

Cited by 236 publications

References 35 publications

Filopodia: Complex models for simple rods

Filopodia: Complex models for simple rods

Progress and perspectives in signal transduction, actin dynamics, and movement at the cell and tissue level: lessons fromDictyostelium

Interaction of the N- and C-terminal Autoregulatory Domains of FRL2 Does Not Inhibit FRL2 Activity

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