ACF7 Regulates Cytoskeletal-Focal Adhesion Dynamics and Migration and Has ATPase Activity

Wu, Xiaoyang; Kodama, Atsuko; Fuchs, Elaine

doi:10.1016/j.cell.2008.07.045

Cited by 260 publications

(419 citation statements)

References 56 publications

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“…Other proteins have been proposed to guide microtubule organization, such as long-lived F-actin structures like stress fibers. Stress fibers interact with microtubules through mammalian spectraplakin ACF-7 and targets microtubules to focal adhesions, thus triggering focal adhesion disassembly and promoting keratinocyte migration (Wu et al, 2008). Similarly, in neuronal growth cones, actin arcs can guide the assembly and transport of microtubules (Schaefer et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Vimentin Intermediate Filaments Template Microtubule Networks to Enhance Persistence in Cell Polarity and Directed Migration

Gan¹,

Ding²,

Burckhardt³

et al. 2016

Cell Systems

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SUMMARYIncreased expression of vimentin intermediate filaments (VIF) enhances directed cell migration, but the mechanism behind VIF's effect on motility is not understood. VIF interact with microtubules, whose organization contributes to polarity maintenance in migrating cells. Here we characterize the dynamic coordination of VIF and microtubule networks in wounded monolayers of Retinal Pigment Epithelial cells. By genome editing we fluorescently labelled endogenous vimentin and α-tubulin and we developed computational image analysis to delineate architecture and interactions of the two networks. Our results show that VIF assemble an ultrastructural copy of the previously polarized microtubule network. Because the VIF network is long-lived compared to the microtubule network, VIF template future microtubule growth along previous microtubule tracks, thus providing a feedback mechanism that maintains cell polarity. VIF knockdown prevents cells from polarizing and migrating properly during wound healing. We suggest that VIF's templating function establishes a memory in microtubule organization that enhances persistence in cell polarization in general and migration in particular.

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Section: Discussionmentioning

confidence: 99%

Vimentin Intermediate Filaments Template Microtubule Networks to Enhance Persistence in Cell Polarity and Directed Migration

Gan¹,

Ding²,

Burckhardt³

et al. 2016

Cell Systems

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“…Components of the cytoskeleton including actin, microtubules, and nonmuscle myosin II are required for sustained directional migration and polarity in a broad range of cell types (25)(26)(27)(28). We assessed the relative contribution of these components on T␤RIII-mediated inhibition of migration by treating Ovca429Neo and Ovca429T␤RIII cells with either cytochalasin D, an inhibitor of actin polymerization; blebbistatin, an inhibitor of nonmuscle myosin II; or nocodazole to disrupt microtubules.…”

Section: T␤riii Regulates the Actin Cytoskeleton Of Cancer And Epithementioning

confidence: 99%

The type III TGF-β receptor regulates epithelial and cancer cell migration through β-arrestin2-mediated activation of Cdc42

Mythreye¹,

Blobe

2009

Proc. Natl. Acad. Sci. U.S.A.

127

139

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Loss of expression of the TGF-␤ superfamily coreceptor, the type III TGF-␤ receptor (T␤RIII or betaglycan), occurs in a broad spectrum of human cancers including breast, lung, ovarian, pancreatic, prostate, and renal cell cancer. T␤RIII suppresses cancer progression in vivo, at least in part, by reducing cancer cell motility. However, the mechanism by which T␤RIII regulates migration is unknown. Here, we demonstrate an unexpected TGF-␤ signaling independent role for T␤RIII in activating Cdc42, altering the actin cytoskeleton and reducing directional persistence to inhibit random migration of both cancer and normal epithelial cells. Functionally, T␤RIII through its interaction with the scaffolding protein ␤-arrestin2, activates Cdc42 and inhibits migration. These studies identify a TGF-␤ independent homeostatic function for T␤RIII in regulating cell migration.C ell migration is a complex process required for physiological functions including embryonic development and wound healing. Alterations in cell migration are also critical to disease pathogenesis, including inflammatory and vascular diseases, tumor cell invasion, and metastases (1, 2). The ability of cells to migrate is regulated both by the speed and the directionality of migration that can be triggered by external cues (i.e., chemotaxis) or because of the intrinsic property of cells to migrate (i.e., intrinsic persistence) that are in turn regulated by the Rho family of GTPases, integrins, the actin cytoskelton, and microtubules (3, 4). Several migratory processes in development and tissue remodeling occur without any evidence of extrinsic chemotactic signaling, relying instead on intrinsic cell migratory properties (5).The type III TGF-␤ receptor (T␤RIII/betaglycan), an 849 aa heparan sulfate proteoglycan, is the most abundant and ubiquitously expressed TGF-␤ superfamily coreceptor. T␤RIII has the potential to increase or decrease TGF-␤ signaling through mechanisms yet to be fully defined (6-8). T␤RIII is classically thought to function as a coreceptor, presenting TGF-␤ superfamily ligands to their respective signaling receptors (8). Recent studies have suggested essential, nonredundant roles for T␤RIII in regulating signaling through T␤RII and T␤RI as well as independently of T␤RII and T␤RI (9). T␤RIII null embryos die on embryonic day 13.5, exhibiting hepatic and cardiovascular defects (10). An essential role for T␤RIII has also been demonstrated in mesenchymal transformation during chick embryonic heart development (11, 12) and in mediating TGF-␤ resistance in intestinal goblet cells (13). We have defined essential roles for the cytoplasmic domain of T␤RIII in mediating TGF-␤ signaling independent of the ligand presentation role (14), along with regulating cell-surface levels of T␤RIII and T␤RII through interactions with G␣-interacting protein-interacting protein, C terminus (GIPC) (15) and ␤-arrestin2 (16).Loss of T␤RIII expression has been reported in multiple cancers, with loss of expression correlating with disease progression, advanced stage, or ...

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“…p0015 Surprisingly, no human diseases or conditions have been associated with MACF1/ACF7, but mouse and zebrafish models suggest its involvement in a wide range of developmental processes, ranging from early embryogenesis (Chen et al, 2006;Gupta et al, 2010), cell migration of fibroblasts, or skin stem cells (Wu, Kodama, & Fuchs, 2008;Wu et al, 2011), as well as heart and brain development (Fassett et al, 2013;Goryunov, He, Lin, Leung, & Liem, 2010;Jorgensen et al, 2014;Sánchez-Soriano et al, 2009 First, in vivo work is relatively fast in flies, and it is not unusual that new experimental ideas yield experimental data within a few weeks. Notably, there are no legal requirements, meaning that experiments can be performed straight off the drawing board with little or no need for an extensive ethical approval process.…”

Section: Article In Pressmentioning

confidence: 99%

Functional and Genetic Analysis of Spectraplakins in Drosophila

Hahn¹,

Ronshaugen²,

Sánchez‐Soriano

et al. 2016

Methods in Enzymology

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ACF7 Regulates Cytoskeletal-Focal Adhesion Dynamics and Migration and Has ATPase Activity

Cited by 260 publications

References 56 publications

Vimentin Intermediate Filaments Template Microtubule Networks to Enhance Persistence in Cell Polarity and Directed Migration

Vimentin Intermediate Filaments Template Microtubule Networks to Enhance Persistence in Cell Polarity and Directed Migration

The type III TGF-β receptor regulates epithelial and cancer cell migration through β-arrestin2-mediated activation of Cdc42

Functional and Genetic Analysis of Spectraplakins in Drosophila

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