Human Spire Interacts with the Barbed End of the Actin Filament

Ito, Toshiro; Narita, Akihiro; Hirayama, Tasuku; Taki, Masayasu; Iyoshi, Shohei; Yamamoto, Yukio; Maéda, Yuichiro; Oda, Tatsuya

doi:10.1016/j.jmb.2010.12.045

Cited by 26 publications

(21 citation statements)

References 29 publications

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“…The binding of one Spire to the penultimate actin subunit suffices to cap barbed ends and agrees with Ito et al (36). In contrast, each of the FH2 hemidimers is able to bind a KIND domain (Fig.…”

Section: Discussionsupporting

confidence: 90%

Role of the C-terminal Extension of Formin 2 in Its Activation by Spire Protein and Processive Assembly of Actin Filaments

Montaville¹,

Kühn²,

Compper

et al. 2016

Journal of Biological Chemistry

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Formin 2 (Fmn2), a member of the FMN family of formins, plays an important role in early development. This formin cooperates with profilin and Spire, a WASP homology domain 2 (WH2) repeat protein, to stimulate assembly of a dynamic cytoplasmic actin meshwork that facilitates translocation of the meiotic spindle in asymmetric division of mouse oocytes. The kinase-like non-catalytic domain (KIND) of Spire directly interacts with the C-terminal extension of the formin homology domain 2 (FH2) domain of Fmn2, called FSI. This direct interaction is required for the synergy between the two proteins in actin assembly. We have recently demonstrated how Spire, which caps barbed ends via its WH2 domains, activates Fmn2. Fmn2 by itself associates very poorly to filament barbed ends but is rapidly recruited to Spire-capped barbed ends via the KIND domain, and it subsequently displaces Spire from the barbed end to elicit rapid processive assembly from profilin⅐actin. Here, we address the mechanism by which Spire and Fmn2 compete at barbed ends and the role of FSI in orchestrating this competition as well as in the processivity of Fmn2. We have combined microcalorimetric, fluorescence, and hydrodynamic binding assays, as well as bulk solution and single filament measurements of actin assembly, to show that removal of FSI converts Fmn2 into a Capping Protein. This activity is mimicked by association of KIND to Fmn2. In addition, FSI binds actin at filament barbed ends as a weak capper and plays a role in displacing the WH2 domains of Spire from actin, thus allowing the association of actin-binding regions of FH2 to the barbed end.Polarized assembly of actin filaments is pivotal in motile processes. It is precisely regulated by proteins that bind the barbed ends of actin filaments and either block or assist filament assembly using various mechanisms (1). Among these regulators, formins are acknowledged to nucleate and track filament barbed ends, mediating rapid processive elongation of filaments (2, 3). In contrast, WASP homology 2 (WH2) 3 repeatcontaining proteins display versatile barbed end capping or tracking and filament severing activities (4). In early oogenesis of Drosophila as well as in mammalian meiosis, a formin (Fmn2/Cappuccino) and a WH2-repeat protein (Spire) synergize in an intriguing fashion to stimulate massive assembly of a dynamic cytoplasmic actin meshwork, required for completion of crucial steps in axis patterning or asymmetric division (5-12). This complexity adds to the known need of profilin for rapid processive assembly of all formins, including Cappuccino (9). Like most formins, Fmn2 harbors conserved C-terminal formin homology 1 (FH1) and formin homology 2 (FH2) domains. The C-terminal FH1-FH2 domain of Fmn2 represents a constitutive active module in which the FH1 domain binds profilin and the FH2 domain to the barbed end of F-actin. The head-to-tail FH2 dimer of formins is thought, from structural data, to encircle the terminal and subterminal actin subunits that constitute the barbed end of the fil...

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Section: Discussionsupporting

confidence: 90%

Role of the C-terminal Extension of Formin 2 in Its Activation by Spire Protein and Processive Assembly of Actin Filaments

Montaville¹,

Kühn²,

Compper

et al. 2016

Journal of Biological Chemistry

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“…9A). The WH2s from N-WASP and Spire exhibit barbed end binding ability, whereas those of Cobl do not (20,21,25,26). Our results show that the barbed end binding affinity for the FMNL3 C terminus is dramatically increased when it is dimeric, approaching the affinity of FMNL3 FH2 domain, although its actin monomer binding affinity remains unchanged.…”

Section: Discussionmentioning

confidence: 71%

“…Similarly, Spire contains four WH2 repeats and is capable of preventing both profilin-actin addition to filaments and barbed end depolymerization with nanomolar potency (20). Although the localization of Spire on actin filaments is still debated, an electron microscopy study suggests barbed end binding (26).…”

mentioning

confidence: 99%

The C Terminus of Formin FMNL3 Accelerates Actin Polymerization and Contains a WH2 Domain-like Sequence That Binds Both Monomers and Filament Barbed Ends

Heimsath

Higgs

2012

Journal of Biological Chemistry

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Background:The mammalian formin FMNL3 influences actin dynamics and promotes filopodia formation. Results: The C terminus of FMNL3 synergizes with the FH2 domain to accelerate actin polymerization, binds actin monomers, and enhances filament severing. Conclusion: The C terminus of FMNL3 contains a WH2-like sequence that binds filament barbed ends and monomers. Significance: The contribution of the C terminus to actin dynamics differs significantly between formins.

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“…Second, in dilution-induced depolymerization assays, in which the core ADP-F-actin subunits dissociate endwise, their interaction with the barbed ends enhances by 7-fold the dissociation of MgADP-F-actin subunits. These data bring growing evidence for a variety of functional interactions of WH2 domains with barbed ends, including the capture of barbed ends by the WH2 domain of N-WASP (66), the capping of barbed ends by Spire WH2 domains (46,67), and the tracking of barbed ends by the WH2 domain of VASP (68,69). Table 3 summarizes the diverse multifunctionality patterns reported on various WH2 repeats.…”

Section: Discussionmentioning

confidence: 99%

Interactions of Isolated C-terminal Fragments of Neural Wiskott-Aldrich Syndrome Protein (N-WASP) with Actin and Arp2/3 Complex

Gaucher

Mauge

Didry

et al. 2012

Journal of Biological Chemistry

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Human Spire Interacts with the Barbed End of the Actin Filament

Cited by 26 publications

References 29 publications

Role of the C-terminal Extension of Formin 2 in Its Activation by Spire Protein and Processive Assembly of Actin Filaments

Role of the C-terminal Extension of Formin 2 in Its Activation by Spire Protein and Processive Assembly of Actin Filaments

The C Terminus of Formin FMNL3 Accelerates Actin Polymerization and Contains a WH2 Domain-like Sequence That Binds Both Monomers and Filament Barbed Ends

Interactions of Isolated C-terminal Fragments of Neural Wiskott-Aldrich Syndrome Protein (N-WASP) with Actin and Arp2/3 Complex

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