Microfilament organization correlates with increased cellular content of gelsolin

Banyard, M. R. C.; Medveczyk, C.J.; Tellam, Ross L.

doi:10.1016/0014-4827(90)90135-w

Cited by 7 publications

(4 citation statements)

References 22 publications

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“…Several structural and regulatory elements of the actin-based microfilament network have been implicated in the cytoarchitectural anomalies which typify ras-transformed cells (Ryan & Higgins, 1988;. These include gelsolin (Fujita et al, 1990;Banyard et al, 1990), vinculin (Burridge, 1986), high-M, tropomyosin (TM1) (Matsumura et al, 1983;Lin et al, 1984) and actin itself (e.g. Leavitt & Kakunaga, 1980).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, although gelsolin does sever and cap actin filaments in vitro, increased microfilament organization typically accompanies aug-Vol. 279 mented gelsolin expression in cultured cells (Banyard et al, 1990;Fujita et al, 1990). Apparent differences between activity in vitro and in vivo may reside in the particular variant of gelsolin and the specific cell type involved.…”

Section: Discussionmentioning

confidence: 99%

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p52(PAI-1) and actin expression in butyrate-induced flat revertants of v-ras-transformed rat kidney cells

Higgins

Ryan

1991

Biochemical Journal

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Flat revertants of v-ras-transformed (KNRK) rat kidney cells, which express elevated levels of p21ras protein, were generated to high efficiencies with sodium butyrate (NaB). Overall protein synthesis in revertants was not different from parental cells, although changes were evident in expression and distribution of specific microfilament-associated cytoskeletal proteins. Quantitative two-dimensional electrophoresis revealed revertant-associated 3-4-fold increases in cytoskeletal deposition of the microfilament-associated proteins gelsolin and vinculin correlating with microfilament reorganization and focal-contact formation respectively. Similar increases in actin content were evident at both the total-cellular- and cytoskeletal-associated-protein levels. In contrast, intermediate-filament family elements (vimentin, lamins) remained unaltered. The only unique protein resolved in flat revertants was p52, a 52 kDa extracellular-matrix-associated protein previously identified as plasminogen-activator inhibitor type 1 (PAI-1). p52(PAI-1) expression was induced early during generation of the revertant phenotype and preceded development of focal-contact structures. NaB-induced p52(PAI-1) synthesis and generation of early morphological reversion in KNRK cells required ongoing RNA synthesis, since exposure to actinomycin D before addition of NaB inhibited both events. p52(PAI-1) induction by NaB was regulated at the level of mRNA abundance; in contrast, actin mRNA levels were the same in parental and revertant cells, suggesting that the increased actin content which typified the revertant phenotype was due to augmented actin microfilament stability.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

p52(PAI-1) and actin expression in butyrate-induced flat revertants of v-ras-transformed rat kidney cells

Higgins

Ryan

1991

Biochemical Journal

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“…Interestingly, if the fibroblasts revert back to a nontransformed state, gelsolin levels increase markedly and these cells cannot then be re-transformed. There also is a direct correlation between gelsolin expression and stress fiber content and an inverse correlation between gelsolin and tumorigenic potential [46]. These changes extended to in vivo immunostained sections of human breast cancers where a sharp decrease in gelsolin staining compared to normal breast tissue was seen [47].…”

Section: Actin Associated Proteins and Malignancymentioning

confidence: 99%

Actin structural proteins in cell motility

Cunningham

1992

Cancer Metast Rev

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The machinery for cell locomotion is based in a network of polymerized actin filaments supporting the peripheral cytoplasm. This network or 'gel' consists of actin filaments in a variety of configurations, including cables, loose bundles, and branching arrays; all formed by the interaction of actin-associated proteins with actin filaments. For cell locomotion to occur, this network must be reversibly disassembled or 'solated' to allow protrusion, then re-assembled to stabilize the resulting extension. Thus, proteins to promote both 'solation' and 'gelation' of actin are important for efficient cell locomotion. Because of their distribution, control, and in vitro effects on actin filaments, two such proteins, gelsolin and actin-binding protein (ABP) should play especially important roles in cell motility. Support for this premise is found in in vivo studies of mouse kidney fibroblasts which demonstrated increased translocational locomotion after cytoplasmic gelsolin expression was increased genetically and in melanoma cells missing actin-binding protein which behave as expected for a cell unable to achieve efficient actin gelation. Since malignant transformation is known to affect the expression and distribution of several of these actin structural proteins, including gelsolin, further investigations of the role these proteins play in cell motility will be important to the determination of tumor cell motility and hence metastatic propensity.

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“…Since significant deviations from normal morphology and substrate adhesion typify the ras-transformed phenotype [1][2][3][4][5], genes that encode proteins that influence cytoskeletal organization and\or adhesive contact structures represent potential functional mediators [4]. Candidates include gelsolin [6,7], vinculin [8], tropomyosin [9], fibronectin and laminin [10], certain integrins [11], actin [12] and the 52 kDa type-1 inhibitor of plasminogen activator (p52 PAI-" ) [4,13] ; each appear to be transformation-sensitive in specific cell systems [4]. Indeed, expression of a specific 92 kDa\pI 5n7 gelsolin variant coincided with morphological reversion in human EJras val-"# -transformed NIH 3T3\R1 cells [6], and increases in gelsolin, vinculin and p52 PAI-" synthesis correlated with cytoarchitectural reorganization in sodium butyrate-induced flat revertants of v-ras-transformed rat kidney (KNRK) cells [4].…”

Section: Introductionmentioning

confidence: 99%

p52PAI-1 gene expression in butyrate-induced flat revertants of v-ras-transformed rat kidney cells: mechanism of induction and involvement in the morphological response

Higgins

Ryan

Jelley

1997

Biochemical Journal

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Sodium n-butyrate-induced flat reversion in v-K-ras oncogene-transformed rat kidney (KNRK) cells is associated with transcriptional activation of the p52PAI-1 gene (which encodes the type-1 inhibitor of plasminogen activator). Butyrate-initiated expression of p52PAI-1 mRNA and protein correlated with induced cell spreading and preceded development of cell-to-substrate focal adhesions. Such undersurface matrix contact structures, which are absent from parental KNRK cells, require proximal PAI-1 deposition for their stabilization. Stimulated p52PAI-1 expression by flat revertants (approximating 25-fold that of control cells) and the accompanying cytoarchitectural reorganization appeared to be programmed responses to butyrate as both events required de novo RNA and protein synthesis, metabolic characteristics consistent with a secondary pathway of gene regulation. To assess the relevance of p52PAI-1 induction to the process of flat reversion more critically, a molecular genetic approach was designed to maintain high-level constitutive p52PAI-1 synthesis in the absence of butyrate. KNRK cells transfected with a Rc/CMVPAI plasmid construct, in which expression of a p52PAI-1 cDNA insert was driven by enhancer-promoter sequences from the immediate-early gene of human cytomegalovirus, formed colonies comprised of flat-revertant-like cells with a greater frequency than did cells transfected with the Rc/CMV vector alone (24.8% and 1.7% respectively). Comparative analysis of randomly selected Rc/ CMVPAI clones indicated that a 10-fold increase in immunoreactive p52PAI-1 protein, relative to Rc/CMV isolates, correlated with generation of the flat phenotype. These data suggest that induced p52PAI-1 expression probably functions in the development of morphological revertants in the KNRK cell system.

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Microfilament organization correlates with increased cellular content of gelsolin

Cited by 7 publications

References 22 publications

p52(PAI-1) and actin expression in butyrate-induced flat revertants of v-ras-transformed rat kidney cells

p52(PAI-1) and actin expression in butyrate-induced flat revertants of v-ras-transformed rat kidney cells

Actin structural proteins in cell motility

p52PAI-1 gene expression in butyrate-induced flat revertants of v-ras-transformed rat kidney cells: mechanism of induction and involvement in the morphological response

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