Binding of gelsolin domain 2 to actin

Renoult, Celine; Blondin, Laurence; Fattoum, Abdellatif; Ternent, Diane; Maciver, Sutherland K.; Raynaud, Fabrice; Benyamin, Yves; Roustan, Claude

doi:10.1046/j.0014-2956.2001.02574.x

Cited by 14 publications

(3 citation statements)

References 57 publications

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“…Gelsolin is an actin-binding protein which severs and caps actin filaments [6], and regulates cytoskeletal turnover. Gelsolin appears to have complex roles in tumor biology, with evidence supporting its contradictory involvement in both tumor suppression as well as malignant progression.…”

Section: Introductionmentioning

confidence: 99%

Gelsolin Induces Colorectal Tumor Cell Invasion via Modulation of the Urokinase-Type Plasminogen Activator Cascade

et al. 2012

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Gelsolin is a cytoskeletal protein which participates in actin filament dynamics and promotes cell motility and plasticity. Although initially regarded as a tumor suppressor, gelsolin expression in certain tumors correlates with poor prognosis and therapy-resistance. In vitro, gelsolin has anti-apoptotic and pro-migratory functions and is critical for invasion of some types of tumor cells. We found that gelsolin was highly expressed at tumor borders infiltrating into adjacent liver tissues, as examined by immunohistochemistry. Although gelsolin contributes to lamellipodia formation in migrating cells, the mechanisms by which it induces tumor invasion are unclear. Gelsolin’s influence on the invasive activity of colorectal cancer cells was investigated using overexpression and small interfering RNA knockdown. We show that gelsolin is required for invasion of colorectal cancer cells through matrigel. Microarray analysis and quantitative PCR indicate that gelsolin overexpression induces the upregulation of invasion-promoting genes in colorectal cancer cells, including the matrix-degrading urokinase-type plasminogen activator (uPA). Conversely, gelsolin knockdown reduces uPA levels, as well as uPA secretion. The enhanced invasiveness of gelsolin-overexpressing cells was attenuated by treatment with function-blocking antibodies to either uPA or its receptor uPAR, indicating that uPA/uPAR activity is crucial for gelsolin-dependent invasion. In summary, our data reveals novel functions of gelsolin in colorectal tumor cell invasion through its modulation of the uPA/uPAR cascade, with potentially important roles in colorectal tumor dissemination to metastatic sites.

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Section: Introductionmentioning

confidence: 99%

Gelsolin Induces Colorectal Tumor Cell Invasion via Modulation of the Urokinase-Type Plasminogen Activator Cascade

et al. 2012

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“…Gelsolin domain G2 is thought to bind to a site on an actin unit within F‐actin in a manner that resembles the interaction between G1 and actin [10,26], as well as making contact with the same actin unit to which G1 ultimately binds [11,27]. Puius et al [10] use this as the basis for a molecular model of how the first two domains of activated gelsolin bind to the barbed end of an actin filament.…”

Section: Resultsmentioning

confidence: 99%

“…So, although the structures of the two halves of gelsolin are similar in the inactive state [6], they are expected to be significantly different once activated. Several investigators have focused attention on the linker between G1 and G2 as a possible pivot point that would allow G2 to move to a position that would be consistent with its role as the F‐actin binding domain of gelsolin [8–12]. The terminal residues of G1 in the structure of G1 bound to monomeric actin [13] point in a direction that suggests G2 may bind to a G1‐type site on actin, but one unit away on the same strand of the long‐pitch actin helix [8].…”

Section: Introductionmentioning

confidence: 99%

From the first to the second domain of gelsolin: a common path on the surface of actin?¹

et al. 2003

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We present the 2.6 A î resolution crystal structure of a complex formed between G-actin and gelsolin fragment Met25Ĝ ln160 (G1+). The structure di¡ers from those of other gelsolin domain 1 (G1) complexes in that an additional six amino acid residues from the crucial linker region into gelsolin domain 2 (G2) are visible and are attached securely to the surface of actin. The linker segment extends away from G1 up the face of actin in a direction that infers G2 will bind along the same long-pitch helical strand as the actin bound to G1. This is consistent with a mechanism whereby G2 attaches gelsolin to the side of a ¢lament and then directs G1 toward a position where it would disrupt actin^actin contacts. Alignment of the sequence of the structurally important residues within the G1^G2 linker with those of WH2 (WASp homology domain 2) domain protein family members (e.g. WASp (Wiscott^Aldridge syndrome protein) and thymosin L L4) suggests that the opposing activities of ¢lament assembly and disassembly may exploit a common patch on the surface of actin. ß

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Microfilaments and microtubules maintain endothelial integrity

Lee

Gotlieb

2002

Microscopy Res & Technique

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The endothelium is a highly metabolic monolayer of cells regulating numerous physiological and pathological functions that maintain the permeability and thromboresistant functions of the endothelium. The structure and function of the endothelial cytoskeleton prevents vascular disease by regulating the structure of the endothelium to act as a resting molecular barrier to atherogenic proteins and by becoming an activated layer of migrating cells to repair denuding injuries. The purpose of this review is to examine the structure of the endothelial cytoskeleton and its roles in cell-cell and cell-substratum adhesion, cell signaling, and regulation of wound repair. Studies focused on the cellular and molecular biology of the structure and function of the endothelial cytoskeleton and in wound repair are reviewed. The cytoskeleton is a key regulator in maintaining endothelial integrity and in restoring integrity following injurious denudation, such as those that occur in the pathogenesis of atherosclerosis. Actin microfilaments and their associated adherens junctions and focal adhesions are important regulators of cell signaling, cell locomotion, cell adhesion, and wound repair mechanisms. Various proteins have been implicated in controlling cytoskeletal-based endothelial function and repair such as tyrosine kinases/phosphatases and the Rho family of proteins. The normal function of the endothelium is highly dependent on the endothelial cytoskeleton. Disruption and dysfunction of the cytoskeleton may result in impairment of endothelial function, subsequently tipping the balance towards vascular disease. Thus, an understanding of the cellular and molecular biology of the endothelial cytoskeleton is essential in our understanding of the pathogenesis of vascular disease, especially atherosclerosis.

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Binding of gelsolin domain 2 to actin

Cited by 14 publications

References 57 publications

Gelsolin Induces Colorectal Tumor Cell Invasion via Modulation of the Urokinase-Type Plasminogen Activator Cascade

Gelsolin Induces Colorectal Tumor Cell Invasion via Modulation of the Urokinase-Type Plasminogen Activator Cascade

From the first to the second domain of gelsolin: a common path on the surface of actin?¹

Microfilaments and microtubules maintain endothelial integrity

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Binding of gelsolin domain 2 to actin

Cited by 14 publications

References 57 publications

Gelsolin Induces Colorectal Tumor Cell Invasion via Modulation of the Urokinase-Type Plasminogen Activator Cascade

Gelsolin Induces Colorectal Tumor Cell Invasion via Modulation of the Urokinase-Type Plasminogen Activator Cascade

From the first to the second domain of gelsolin: a common path on the surface of actin?1

Microfilaments and microtubules maintain endothelial integrity

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From the first to the second domain of gelsolin: a common path on the surface of actin?¹