Specific interaction between phosphatidylinositol 4,5-bisphosphate and profilactin

Lassing, Ingrid; Lindberg, Uno

doi:10.1038/314472a0

Cited by 817 publications

(502 citation statements)

References 37 publications

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“…Originally identified as an actin-monomer sequestering protein, profilin was subsequently shown to enhance the rate of nucleotide exchange on actin and to retard the rate of hydrolysis of bound ATP [1,2]. Profilin also irtteracts with the acidic phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) in vitro, which has the combined effects of blocking profilin-actin interactions and preventing PIP2 cleavage by unphosphorylated (unactivated) phospholipase C'fl [3][4][5][6]. This has led to the hypothesis that profilin may play a key role in linking signal transduction pathways to control of the actin cytoskeleton.…”

Section: Yeast Strains and Culture Conditionsmentioning

confidence: 99%

Profilin is required for the normal timing of actin polymerization in response to thermal stress

Yeh

Haarer

1996

FEBS Letters

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We have used a fluorometric assay to determine the relative amounts of polymerized actin (F-actin) in wild-type and profilin mutant yeast cells. Our results indicate that profilin plays a role in maintaining normal F-actin levels in response to shifts to high temperature. Cells lacking prof'din display a greater drop in F-actin levels upon such temperature shifts, and are slower to recover to initial F-actin levels than are wild-type cells. Interestingly, shifts to cold temperatures result in rapid increases of F-actin levels in wild-type and profilin null cells. We have further determined that shifting to high-osmolarity growth conditions causes a relatively slow decrease in F-actin levels in wild-type cells, and a small but rapid increase in the F-actin levels in profilin null cells. Profilin null cells contain normal concentrations of F-actin while growing exponentially at room temperature, indicating that profilin is not essential for maintaining F-actin concentrations during steady-state growth. Our data suggest that actin is inherently unstable in vivo at high temperatures, and that profilin helps to maintain actin in its filamentous state at these temperatures, perhaps by stimulating actin polymerization in a proper temporal and spatial fashion. direct interaction between yeast profilin and adenylate cyclase (S. Palmieri and B. Haarer, unpublished data).Despite these many interactions attributed to profilins from various species, it is still unclear which roles are central to profilin function, and how such properties relate to the in vivo control of the actin cytoskeleton. Convincing arguments can be made for an in vivo role as an inhibitor [13][14][15], or stimulator [8,16] of actin polymerization. Indeed, it is entirely likely that profilin could be playing both roles, depending on species, cell type, or temporal regulation within an individual cell. To further address profilin's potential in vivo functions, we have utilized a fluorometric assay to measure the relative filamentous actin content in cells before and after changing growth conditions. Our findings are consistent with profilin's playing a significant role in the stimulation of actin polymerization under conditions that are perturbing to the yeast actin cytoskeleton. Materials and methods

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Section: Yeast Strains and Culture Conditionsmentioning

confidence: 99%

Profilin is required for the normal timing of actin polymerization in response to thermal stress

Yeh

Haarer

1996

FEBS Letters

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“…The actin-binding protein, profllin, is implicated in the regulation of actin polymerization [l] and the hydrolysis of phosphatidylinositol- (4,5)-bisphosphate (PIP2) [2,3]. These functions of profilin link the dynamics of the microfilament system to processes involved in transmembrane signalling and may be part of the mechanisms behind the immediate mobilization of the microfllament system upon stimulation of cells with growth factors like epidermal growth factor and platelet-derived growth factor [4].…”

Section: Introductionmentioning

confidence: 99%

Mutagenesis of human profilin locates its poly(l‐prolme)‐bindmg site to a hydrophobic patch of aromatic amino acids

et al. 1993

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The actin-binding protein, profilin, contains a src-homology (SH) 3-like fold (Schutt, C.E. et al., submitted), and its tight interaction with poly(L-proline) is reminiscent of the binding activity exhibited by SH3-domains. Here we demonstrate that replacements of aromatic amino acids in a hydrophobic patch on the surface of the protilin molecule abolish its poly(L-proline)-binding capacity. However, the location of this hydrophobic patch is found in another region of the molecule than that displaying structural similarities with SH3 domains.

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“…17 However, not all profilin is necessarily available for binding to actin, as profilin has over 50 identified binding partners, 58 and in particular, it has been demonstrated that binding to phosphoinositides dissociates profiling-actin complexes. 30 Here we vary the effective concentration of profilin from 0 lM to 20 lM to simulate regulation.…”

Section: Parameter Choicesmentioning

confidence: 99%

“…For example, profilin has been shown to associate with the membrane phosphoinositides PIP and PIP 2 and this binding both localizes profilin to the plasma membrane 40 and inhibits actin binding. 30 So, it is certainly possible there actually was very little free profilin available in the cytoplasm of the endothelial cells to influence the bulk actin cycle.…”

Section: Model Agreements and Shortcomingsmentioning

confidence: 99%

Relationships between Actin Regulatory Mechanisms and Measurable State Variables

Bindschadler

McGrath

2007

Ann Biomed Eng

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Abstract-In this report we extend our recent mathematical formulation of the actin cycle model [Bindschadler et al. Biophys. J. 86 (2004) 2720] to predict the influence of key regulatory mechanisms on network-scale state variables estimable in live cell experiments. Specifically, we examine the influence of regulation by cofilin, profilin, capping protein and proteins that adjust filament number through nucleation and/or filament severing, on the higher order variables of average filament length, polymer fraction, and filament turnover rate. Importantly, we find that severing/ nucleation, the acceleration of ADP-subunit disassembly by cofilin, and the catalytic and shuttle functions of profilin have Ôsignature' effects on the higher order state variables. In this way, measurement of the state variables in live cells can allow inference of regulatory mechanism(s) underlying changes in cell state. Our results compare favorably to published data for endothelial cells undergoing a transition from non-motile confluent cells to highly motile subconfluent cells. The extension of our model to higher order state variables allows us to investigate other important issues such as the distinction between basic and higher order measures of filament dynamics, the influence of thymosin b4 on network state variables, the interplay between thymosin b4 and profilin, and the synergystic effects of cofilin and profilin.

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Specific interaction between phosphatidylinositol 4,5-bisphosphate and profilactin

Cited by 817 publications

References 37 publications

Profilin is required for the normal timing of actin polymerization in response to thermal stress

Profilin is required for the normal timing of actin polymerization in response to thermal stress

Mutagenesis of human profilin locates its poly(l‐prolme)‐bindmg site to a hydrophobic patch of aromatic amino acids

Relationships between Actin Regulatory Mechanisms and Measurable State Variables

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