Harnessing actin dynamics for clathrin-mediated endocytosis. Nat Rev Mol Cell Biol 7:404-414

Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3202, USA.
Nature Reviews Molecular Cell Biology (Impact Factor: 37.81). 07/2006; 7(6):404-14. DOI: 10.1038/nrm1940
Source: PubMed


Actin polymerization often occurs at the plasma membrane to drive the protrusion of lamellipodia and filopodia at the leading edge of migrating cells. A role for actin polymerization in another cellular process that involves the reshaping of the plasma membrane--namely endocytosis--has recently been established. Live-cell imaging studies are shedding light on the order and timing of the molecular events and mechanisms of actin function during endocytosis.

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Available from: Christopher Pierre Toret, Oct 02, 2015
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    • "Actin filament assembly can generate mechanical forces to induce membrane deformation (Kaksonen et al., 2006) and to facilitate vesicle trafficking, providing a platform to affect receptor turnover (Zech et al., 2012). It is not clear whether formins being the largest group of actin nucleation and assembly factors play a role in integrin traffic and function. "
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    ABSTRACT: Regulated turnover of integrin receptors is essential for cell adhesion and migration. Pathways selectively regulating β1-integrin recycling are implicated in cancer invasion and metastasis, yet proteins required for the internalization of this pro-invasive integrin remain to be identified. Here, we uncover formin-like 2 (FMNL2) as a critical regulator of β1-integrin internalization downstream of protein kinase C (PKC). PKCα associates with and phosphorylates FMNL2 at S1072 within its Diaphanous autoregulatory region, leading to the release of formin autoinhibition. Phosphorylation of FMNL2 triggers its rapid relocation and promotes its interaction with the cytoplasmic tails of the α-integrin subunits for β1-integrin endocytosis. FMNL2 drives β1-integrin internalization and invasive motility in a phosphorylation-dependent manner, while a FMNL2 mutant defective in actin assembly interferes with β1-integrin endocytosis and cancer cell invasion. Our data establish a role for FMNL2 in the regulation of β1-integrin and provide a mechanistic understanding of the function of FMNL2 in cancer invasiveness. Copyright © 2015 Elsevier Inc. All rights reserved.
    Developmental Cell 08/2015; DOI:10.1016/j.devcel.2015.06.015 · 9.71 Impact Factor
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    • "Arcs do not directly associate with focal adhesions but are linked to these cell-matrix interaction sites through ''dorsal stress fibers'' (radial fibers), which are non-contractile actin bundles connected to focal adhesions at their distal end (Tojkander et al., 2012; Burridge and Wittchen, 2013). Furthermore, eukaryotic cells contain an array of other actin-based structures that contribute to diverse cellular processes such as endocytosis, mitochondrial fission, and extracellular matrix degradation (Kaksonen et al., 2006; Schoumacher et al., 2010; Korobova et al., 2013). Importantly, actin filaments do not function in isolation but collaborate with two other cytoskeletal networks: intermediate filaments and microtubules (Huber et al., 2015). "
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    ABSTRACT: The actin cytoskeleton and cytoplasmic intermediate filaments contribute to cell migration and morphogenesis, but the interplay between these two central cytoskeletal elements has remained elusive. Here, we find that specific actin stress fiber structures, transverse arcs, interact with vimentin intermediate filaments and promote their retrograde flow. Consequently, myosin-II-containing arcs are important for perinuclear localization of the vimentin network in cells. The vimentin network reciprocally restricts retrograde movement of arcs and hence controls the width of flat lamellum at the leading edge of the cell. Depletion of plectin recapitulates the vimentin organization phenotype of arc-deficient cells without affecting the integrity of vimentin filaments or stress fibers, demonstrating that this cytoskeletal cross-linker is required for productive interactions between vimentin and arcs. Collectively, our results reveal that plectin-mediated interplay between contractile actomyosin arcs and vimentin intermediate filaments controls the localization and dynamics of these two cytoskeletal systems and is consequently important for cell morphogenesis. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Cell Reports 05/2015; 11(10). DOI:10.1016/j.celrep.2015.05.008 · 8.36 Impact Factor
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    • "Although actin is dispensable for the process of endocytosis in higher eukaryotes, several studies have indicated an important regulatory role for actin in integrin endosomal traffic particularly on endosomes. Actin-related protein (Arp)2/3, a multiprotein complex and actin nucleator, promotes the assembly of branched F-actin networks at the plasma membrane and on endosomes (Goley and Welch, 2006; Kaksonen et al., 2006). Activation of Arp2/3 is mediated by nucleation-promoting factors such as members of the Wiskott– Aldrich syndrome protein (WASP) family, all of which function in distinct subcellular locations (reviewed in Takenawa and Suetsugu, 2007). "
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    ABSTRACT: Integrins are a family of transmembrane cell surface molecules that constitute the principal adhesion receptors for the extracellular matrix (ECM) and are indispensable for the existence of multicellular organisms. In vertebrates, 24 different integrin heterodimers exist with differing substrate specificity and tissue expression. Integrin-extracellular-ligand interaction provides a physical anchor for the cell and triggers a vast array of intracellular signalling events that determine cell fate. Dynamic remodelling of adhesions, through rapid endocytic and exocytic trafficking of integrin receptors, is an important mechanism employed by cells to regulate integrin-ECM interactions, and thus cellular signalling, during processes such as cell migration, invasion and cytokinesis. The initial concept of integrin traffic as a means to translocate adhesion receptors within the cell has now been expanded with the growing appreciation that traffic is intimately linked to the cell signalling apparatus. Furthermore, endosomal pathways are emerging as crucial regulators of integrin stability and expression in cells. Thus, integrin traffic is relevant in a number of pathological conditions, especially in cancer. Nearly a decade ago we wrote a Commentary in Journal of Cell Science entitled 'Integrin traffic'. With the advances in the field, we felt it would be appropriate to provide the growing number of researchers interested in integrin traffic with an update.
    Journal of Cell Science 02/2015; 128(5). DOI:10.1242/jcs.161653 · 5.43 Impact Factor
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