Dia-Interacting Protein Modulates Formin-Mediated Actin Assembly at the Cell Cortex

Eisenmann, Kathryn M.; Harris, Elizabeth S.; Kitchen, Susan M.; Holman, Holly A.; Higgs, Henry N.; Alberts, Arthur S.

doi:10.1016/j.cub.2007.03.024

Cited by 115 publications

(111 citation statements)

References 39 publications

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“…The 'activated' mDia1 could then bind to its other partners, such as POPX2. A similar observation has been reported for mDia2 and DIP, whereby the binding of CDC42 to mDia2 relieves the auto-inhibition of mDia2 and allows its interaction with DIP (Eisenmann et al, 2007). Thus, the interaction of mDia1 with POPX2 might provide a mechanism for fine modulation of mDia1 activity.…”

Section: Discussionsupporting

confidence: 78%

Functional interactions between phosphatase POPX2 and mDia modulate RhoA pathways

Xie

Tan

Wee

et al. 2008

Journal of Cell Science

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Rho GTPases and their downstream effectors regulate changes in the actin cytoskeleton that underlie cell motility and adhesion. They also participate, with RhoA, in the regulation of gene transcription by activating serum response factor (SRF)-mediated transcription from the serum response element (SRE). SRF-mediated transcription is also promoted by several proteins that regulate the polymerization or stability of actin. We have previously identified a family of PP2C phosphatases, POPXs, which can dephosphorylate the CDC42/RAC-activated kinase PAK and downregulate its enzymatic and actin cytoskeletal activity. We now report that POPX2 interacts with the formin protein mDia1 (DIAPH1). This interaction is enhanced when mDia1 is activated by RhoA.The binding of POPX2 to mDia1 or to an mDia-containing complex greatly decreases the ability of mDia1 to activate transcription from the SRE. We propose that the interaction between mDia1 and POPX2 (PPM1F) serves to regulate both the actin cytoskeleton and SRF-mediated transcription, and to link the CDC42/RAC1 pathways with those of RhoA. Supplementary material available online at

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Section: Discussionsupporting

confidence: 78%

Functional interactions between phosphatase POPX2 and mDia modulate RhoA pathways

Xie

Tan

Wee

et al. 2008

Journal of Cell Science

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“…Only few studies previously addressed the involvement of specific actin nucleators in PM blebbing. Using experimental systems in which PM blebbing was induced by genetic manipulation or protein overexpression, nucleators such as mDia1, mDia2, FHOD1, Arp2/3 that are also involved in the regulation of diverse additional cellular actin remodeling events were implicated in blebbing [12,[41][42][43]. In this present study, we conducted a comprehensive analysis of the involvement of endogenously expressed human actin nucleators in PM blebbing of adhering HeLa cells.…”

Section: Discussionmentioning

confidence: 99%

Differing and isoform-specific roles for the formin DIAPH3 in plasma membrane blebbing and filopodia formation

et al. 2011

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Plasma membrane (PM) blebs are dynamic actin-rich cell protrusions that occur, e.g., during cytokinesis, amoeboid cell motility and cell attachment. Using a targeted siRNA screen against 21 actin nucleation factors, we identify a novel and essential role of the human diaphanous formin DIAPH3 in PM blebbing during cell adhesion. Suppression of DIAPH3 inhibited blebbing to promote rapid cell spreading involving β1-integrin. Multiple isoforms of DIAPH3 were detected on the mRNA and protein level of which isoforms 3 and 7 were the largest and most abundant isoforms that however did not induce formation of actin-rich protrusions. Rather, PM blebbing specifically involved the low abundance isoform 1 of DIAPH3 and activation of isoform 7 by deletion of the diaphanous-autoregulatory domain caused the formation of filopodia. Dimerization and actin assembly activity were essential for induction of specific cell protrusions by DIAPH3 isoforms 1 and 7. Our data suggest that the N-terminal region comprising the GTPasebinding domain determined the subcellular localization of the formin as well as its protrusion activity between blebs and filopodia. We propose that isoform-selective actin assembly by DIAPH3 exerts specific and differentially regulated functions during cell adhesion and motility.

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“…Much less is understood about the regulation of this F-actin network; nonetheless it is clear that RhoA and the ROCK kinases are critical for its maintenance. In addition, it has recently been shown that modulation of Dia2 [20] and PDK1 [97,98] activity can affect cortical actin. High levels of RhoA, RhoC or ROCK activity promote contraction of the cortical actin that is associated with membrane blebbing [99].…”

Section: Actin Organisation In Complex Environmentsmentioning

confidence: 99%

“…Like WAVE and WASP family proteins, FH proteins also switch between an auto-inhibited 'closed' conformation and an active 'open' conformation [6]. Interaction with numerous GTP-binding proteins, including Cdc42, RhoA, RhoB and Rif, and adaptor proteins such as DIP/WISH can stabilise the open conformation thereby promoting actin polymerization driven by the FH2 domain [18][19][20][21][22]. Structural studies indicate that FH2 domains function as dimers with one FH2 domain binding a monomer in the existing actin filament and the other FH2 domain recruiting a new G-actin monomer for polymerisation [23].…”

mentioning

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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Dia-Interacting Protein Modulates Formin-Mediated Actin Assembly at the Cell Cortex

Cited by 115 publications

References 39 publications

Functional interactions between phosphatase POPX2 and mDia modulate RhoA pathways

Functional interactions between phosphatase POPX2 and mDia modulate RhoA pathways

Differing and isoform-specific roles for the formin DIAPH3 in plasma membrane blebbing and filopodia formation

The actin cytoskeleton in cancer cell motility

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