The Schizosaccharomyces pombe cdc3+ gene encodes a profilin essential for cytokinesis.

Balasubramanian, Mohan K.; Hirani, B.; Burke, John D.; Gould, Kathleen L.

doi:10.1083/jcb.125.6.1289

Cited by 221 publications

(235 citation statements)

References 37 publications

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“…Previous studies showed diverse cellular effects of overexpressed or microinjected Pfn1, where in some cases an increase in the overall F-actin content was noticed (Finkel et al, 1994) and in others depolymerisation of existing actin filaments occurred (as could be expected from its G-actin-sequestering property - Balasubramanian et al, 1994). This demonstrates the complexity and cell-type specificity of Pfn1's action on actin cytoskeleton.…”

Section: Pfn1 Overexpression Reorganises Actin Cytoskeleton and Upregmentioning

confidence: 69%

Profilin-1 is a negative regulator of mammary carcinoma aggressiveness

et al. 2007

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Expression of profilin-1 (Pfn1) is downregulated in breast cancer cells, the functional significance of which is yet to be understood. To address this question, in this study we evaluated how perturbing Pfn1 affects motility and invasion of breast cancer cells. We show that loss of Pfn1 expression leads to enhanced motility and matrigel invasiveness of MDA-MB-231 breast cancer cells. Interestingly, silencing Pfn1 expression is associated with downregulation of both cell -cell and cell -matrix adhesions with concomitant increase in motility and dramatic scattering of normal human mammary epithelial cells. Thus, these data for the first time suggest that loss of Pfn1 expression may have significance in breast cancer progression. Consistent with these findings, even a moderate overexpression of Pfn1 induces actin stress-fibres, upregulates focal adhesion, and dramatically inhibits motility and matrigel invasiveness of MDA-MB-231 cells. Using mutants of Pfn1 that are defective in binding to either actin or proline-rich ligands, we further show that overexpressed Pfn1 must have a functional actin-binding site to suppress cell motility. Finally, animal experiments reveal that overexpression of Pfn1 suppresses orthotopic tumorigenicity and micro-metastasis of MDA-MB-231 cells in nude mice. These data imply that perturbing Pfn1 could be a good molecular strategy to limit the aggressiveness of breast cancer cells.

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Section: Pfn1 Overexpression Reorganises Actin Cytoskeleton and Upregmentioning

confidence: 69%

Profilin-1 is a negative regulator of mammary carcinoma aggressiveness

et al. 2007

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“…h Ϫ cdc3-6 P. Nurse (Nurse et al, 1976;Balasubramanian et al, 1994 (Chang et al, 1997;Eng et al, 1998) Bähler and Pringle, 1998 JB23 h Ϫ cdc14-118 leu1-32 P. Nurse (Nurse et al, 1976) (Minet et al, 1979) Hiraoka et al, 1984 a Derived by mating two haploid strains obtained from J. Kohli. b myo2-E1 was originally referred to as rng5-E1 (Balasubramanian et al, 1998;Eng et al, 1998).…”

Section: Jb24mentioning

confidence: 99%

“…Thus, both Ain1p-GFP and GFP-Ain1p appear to provide normal Ain1p function. et al, 1976; McCollum et al, 1995) JB24 h Ϫ cdc3-6 P. Nurse (Nurse et al, 1976;Balasubramanian et al, 1994…”

Section: Molecular Biology Of the Cell 1062mentioning

confidence: 99%

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Roles of a Fimbrin and an α-Actinin-like Protein in Fission Yeast Cell Polarization and Cytokinesis

Bähler

Pringle

2001

MBoC

146

183

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Eukaryotic cells contain many actin-interacting proteins, including the ␣-actinins and the fimbrins, both of which have actin cross-linking activity in vitro. We report here the identification and characterization of both an ␣-actinin-like protein (Ain1p) and a fimbrin (Fim1p) in the fission yeast Schizosaccharomyces pombe. Ain1p localizes to the actomyosin-containing medial ring in an F-actindependent manner, and the Ain1p ring contracts during cytokinesis. ain1 deletion cells have no obvious defects under normal growth conditions but display severe cytokinesis defects, associated with defects in medial-ring and septum formation, under certain stress conditions. Overexpression of Ain1p also causes cytokinesis defects, and the ain1 deletion shows synthetic effects with other mutations known to affect medial-ring positioning and/or organization. Fim1p localizes both to the cortical actin patches and to the medial ring in an F-actin-dependent manner, and several lines of evidence suggest that Fim1p is involved in polarization of the actin cytoskeleton. Although a fim1 deletion strain has no detectable defect in cytokinesis, overexpression of Fim1p causes a lethal cytokinesis defect associated with a failure to form the medial ring and concentrate actin patches at the cell middle. Moreover, an ain1 fim1 double mutant has a synthetical-lethal defect in medial-ring assembly and cell division. Thus, Ain1p and Fim1p appear to have an overlapping and essential function in fission yeast cytokinesis. In addition, protein-localization and mutant-phenotype data suggest that Fim1p, but not Ain1p, plays important roles in mating and in spore formation. INTRODUCTIONThe actin cytoskeleton is involved in many processes in eukaryotic cells, including the polarization of cell growth and cytokinesis. These many roles involve the interaction of actin with a wide variety of actin-binding proteins, including proteins that can cross-link actin filaments into isotropic gels or bundles. Many actin cross-linking proteins have been purified and studied in vitro, but their functions in vivo remain poorly understood (reviewed by Matsudaira, 1994a;Otto, 1994;Furukawa and Fechheimer, 1997;Ayscough, 1998;Bartles, 2000).Among the actin cross-linking proteins, one of the best characterized is ␣-actinin. It was first isolated from rabbit skeletal muscle (Ebashi and Ebashi, 1965) and has subsequently been identified in both muscle and nonmuscle cells from a variety of animals, in Acanthamoeba, and in Dictyostelium (Furukawa and Fechheimer, 1997;Critchley and Flood, 1999). ␣-Actinin forms a homodimer of antiparallel polypeptides (Critchley and Flood, 1999;Djinovic-Carugo et al., 1999), with the actin-binding domain of each polypeptide close to the NH 2 terminus, followed by four spectrin-like repeats and two COOH-terminal EF-hand motifs. Skeletal muscle isoforms are localized to the Z-disk and are not regulated by Ca 2ϩ , whereas nonmuscle isoforms are localized to focal adhesions, stress fibers, and other structures and are typically regulated by C...

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“…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.…”

mentioning

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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The Schizosaccharomyces pombe cdc3+ gene encodes a profilin essential for cytokinesis.

Cited by 221 publications

References 37 publications

Profilin-1 is a negative regulator of mammary carcinoma aggressiveness

Profilin-1 is a negative regulator of mammary carcinoma aggressiveness

Roles of a Fimbrin and an α-Actinin-like Protein in Fission Yeast Cell Polarization and Cytokinesis

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

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