EGF-induced PIP2 hydrolysis releases and activates cofilin locally in carcinoma cells

Rheenen, Jacco van; Song, Xian‐Rong; Roosmalen, Wies van; Cammer, Michael; Chen, Xiaoming; DesMarais, Vera; Yip, Shu Chin; Backer, Jonathan M.; Eddy, Robert J.; Condeelis, John S.

doi:10.1083/jcb.200706206

Cited by 216 publications

(255 citation statements)

References 43 publications

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“…Upon addition of rapamycin, rapid reduction of PI(4,5)P 2 and concurrent formation of membrane protrusion were observed ( Fig. 4A and supplemental Video 2), consistent with a recent finding that PLC-dependent PI(4,5)P 2 hydrolysis induced lamellipodia formation (9). This treatment again induced a translocation of Coronin 1A to the extending lamellipodia ( Fig.…”

Section: Pi(45)p 2 Reduction Induces a Translocation Of Coronin 1a Tsupporting

confidence: 90%

“…A recent study has reported that Coronin 1B coordinates the activities of Arp2/3 complex and cofilin by recruiting Slingshot, which dephosphorylates and thus activates cofilin (13). In addition, Cofilin is inactivated at the plasma membrane by binding to PI(4,5)P 2 (9). In light of these findings, we propose a plausible mechanism to explain how the cooperated activities of these two actin-depolymerizing factors are spatially and temporally regulated by PI(4,5)P 2 (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the activity of ABPs have thought to be inhibited by PI(4,5)P 2 binding that occludes F-actin-binding sites and to be activated by PI(4,5)P 2 hydrolysis when phospholipase C (PLC) is activated by receptor stimulation (5). Indeed, recent in vivo study have reported that Cofilin, an actin-severing protein, is inactivated at the plasma membrane in complex with PI(4,5)P 2 instead of F-actin in resting cells (9).…”

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confidence: 99%

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Proteome of Acidic Phospholipid-binding Proteins

Tsujita

Itoh

Kondo

et al. 2010

Journal of Biological Chemistry

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Reversible interactions between acidic phospholipids in the cellular membrane and proteins in the cytosol play fundamental roles in a wide variety of physiological events. Here, we present a novel approach to the identification of acidic phospholipid-binding proteins using nano-liquid chromatography-tandem mass spectrometry. We found more than 400 proteins, including proteins with previously known acidic phospholipid-binding properties, and confirmed that several candidates, such as Coronin 1A, mDia1 (Diaphanous-related formin-1), PIR121/CYFIP2, EB2 (end plus binding protein-2), KIF21A (kinesin family member 21A), eEF1A1 (translation elongation factor 1␣1), and TRIM2, directly bind to acidic phospholipids. Among such novel proteins, we provide evidence that Coronin 1A activity, which disassembles Arp2/3-containing actin filament branches, is spatially and temporally regulated by phosphatidylinositol 4,5-bisphosphate (PI(4,5)P 2 ). Whereas Coronin 1A co-localizes with PI(4,5)P 2 at the plasma membrane in resting cells, it is dissociated from the plasma membrane during lamellipodia formation where the PI(4,5)P 2 signal is significantly reduced. Our in vitro experiments show that Coronin 1A preferentially binds to PI(4,5)P 2 -containing liposomes and that PI(4,5)P 2 antagonizes the ability of Coronin 1A to disassemble actin filament branches, indicating a spatiotemporal regulation of Coronin 1A via a direct interaction with the plasma membrane lipid. Collectively, our proteomics data provide a list of potential acidic phospholipid-binding protein candidates ranging from the actin regulatory proteins to translational regulators.

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Section: Pi(45)p 2 Reduction Induces a Translocation Of Coronin 1a Tsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Proteome of Acidic Phospholipid-binding Proteins

Tsujita

Itoh

Kondo

et al. 2010

Journal of Biological Chemistry

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“…A localized increase in cofilin activity leads to increased numbers of barbed ends for actin polymerization while Arp2/3 promote the nucleation of new filaments [34,35]. Cofilin activity is localized to a region close the plasma membrane because this is the site where PIP2 is hydrolysed and because of its intrinsic preference for recently polymerised ATP-actin filaments [36], while activation of membrane tethered small G proteins leads to increased Arp2/3 activity at the plasma membrane [37,38]. It should also be noted that in other contexts (such as if ADP-actin filaments are severed or other co-operating mechanism are not active) cofilin-mediated filament severing can reduce F-actin levels.…”

Section: Co-operation and Plasticity In Actin Polymerization Mechanismsmentioning

confidence: 99%

The actin cytoskeleton in cancer cell motility

Olson

Sahai

2008

Clin Exp Metastasis

492

392

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Cancer cell metastasis is a multi-stage process involving invasion into surrounding tissue, intravasation, transit in the blood or lymph, extravasation, and growth at a new site. Many of these steps require cell motility, which is driven by cycles of actin polymerization, cell adhesion and acto-myosin contraction. These processes have been studied in cancer cells in vitro for many years, often with seemingly contradictory results. The challenge now is to understand how the multitude of in vitro observations relates to the movement of cancer cells in living tumour tissue. In this review we will concentrate on actin protrusion and acto-myosin contraction. We will begin by presenting some general principles summarizing the widely-accepted mechanisms for the co-ordinated regulation of actin polymerization and contraction. We will then discuss more recent studies that investigate how experimental manipulation of actin dynamics affects cancer cell invasion in complex environments and in vivo.

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“…Furthermore, severed filaments are the preferred substrate for dendritic nucleation by the Arp complex (8,9). Localized induction of actin polymerization and the formation of branched actin networks constitute the basis for membrane protrusion and cell motility (2,10,11). In line with an upstream regulatory role in the control of these processes, PKD1 and -2 are also capable of binding to F-actin in vitro (1).…”

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confidence: 99%

Protein Kinase D Controls Actin Polymerization and Cell Motility through Phosphorylation of Cortactin

Eiseler

Haußer

Kimpe

et al. 2010

Journal of Biological Chemistry

121

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We here identify protein kinase D (PKD) as an upstream regulator of the F-actin-binding protein cortactin and the Arp actin polymerization machinery. PKD phosphorylates cortactin in vitro and in vivo at serine 298 thereby generating a 14-3-3 binding motif. In vitro, a phosphorylation-deficient cortactin-S298A protein accelerated VCA-Arp-cortactin-mediated synergistic actin polymerization and showed reduced F-actin binding, indicative of enhanced turnover of nucleation complexes. In vivo, cortactin co-localized with the nucleation promoting factor WAVE2, essential for lamellipodia extension, in the actin polymerization zone in Heregulin-treated MCF-7 cells. Using a 3-dye FRET-based approach we further demonstrate that WAVE2-Arp and cortactin prominently interact at these structures. Accordingly, cortactin-S298A significantly enhanced lamellipodia extension and directed cell migration. Our data thus unravel a previously unrecognized mechanism by which PKD controls cancer cell motility.The mechanistic elucidation of signaling pathways regulating dynamic actin remodeling processes in migrating cells is pivotal to a comprehensive understanding of cancer cell metastasis. Protein kinase D (PKD) 2 has recently been identified as a vital upstream regulator of polarized cell motility and F-actin organization (1-4). PKD localizes to sites of dynamic actin remodeling (1). The kinase activity is essential for the control of directed cell motility (1, 2), whereby active PKD1 inhibited, whereas kinase-inactive PKD1KD strongly enhanced motility and invasiveness (1-4). Mechanistically, a key role for PKD1 in controlling the activity of the ubiquitous F-actin depolymerizing-and severing factor cofilin via slingshot1L (SSH1L) cofilin phosphatase has been demonstrated. The activity of SSH1L is mainly regulated by its binding to filamentous actin (F-actin), which has been shown to strongly enhance its activity (5, 6). Phosphorylation of SSH1L at Ser 978 by active PKD1, e.g. downstream of RhoA or oxidative stress, generates a 14-3-3 binding motif within an important F-actin binding region, thus resulting in the sequestration of SSH1L away from dynamic actin structures, reducing SSH1 activity and active non-S3-phosphorylated cofilin levels (2). By severing actin filaments, cofilin increases both the availability of G-actin monomers as well as the number of "barbed ends" for polymerization (7). Furthermore, severed filaments are the preferred substrate for dendritic nucleation by the Arp complex (8, 9). Localized induction of actin polymerization and the formation of branched actin networks constitute the basis for membrane protrusion and cell motility (2, 10, 11). In line with an upstream regulatory role in the control of these processes, PKD1 and -2 are also capable of binding to F-actin in vitro (1). In the case of PKD1, in vivo F-actin binding has been demonstrated as well, which most likely facilitates an interaction with actin regulatory proteins such as SSH1L (2). We now have identified a second key regulatory signaling pathway ...

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EGF-induced PIP2 hydrolysis releases and activates cofilin locally in carcinoma cells

Cited by 216 publications

References 43 publications

Proteome of Acidic Phospholipid-binding Proteins

Proteome of Acidic Phospholipid-binding Proteins

The actin cytoskeleton in cancer cell motility

Protein Kinase D Controls Actin Polymerization and Cell Motility through Phosphorylation of Cortactin

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