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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    • "Down-regulation of Ag uptake activity during the transition from actively sampling immature DCs to uptake-inactive mature DCs has been linked to a loss of active Cdc42 during DC maturation (Garrett et al., 2000). However, receptor-mediated endocytosis depends on the cooperation of actin filaments with other proteins, such as clathrin, for internalization (Schafer, 2002; Kaksonen et al., 2006) and is therefore independent of RhoGTPases and not down-regulated in mature DCs (Garrett et al., 2000; Platt et al., 2010). This allows efficient internalization of exogenous Ag's upon binding to surface receptors during all stages of DC maturation (Allenspach et al., 2008; Platt et al., 2010). "
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    ABSTRACT: Cell division cycle 42 (Cdc42) is a member of the Rho guanosine triphosphatase family and has pivotal functions in actin organization, cell migration, and proliferation. To further study the molecular mechanisms of dendritic cell (DC) regulation by Cdc42, we used Cdc42-deficient DCs. Cdc42 deficiency renders DCs phenotypically mature as they up-regulate the co-stimulatory molecule CD86 from intracellular storages to the cell surface. Cdc42 knockout DCs also accumulate high amounts of invariant chain major histocompatibility complex (MHC) class II complexes at the cell surface, which cannot efficiently present peptide antigens (Ag's) for priming of Ag-specific CD4 T cells. Proteome analyses showed a significant reduction in lysosomal MHC class II processing proteins, such as cathepsins, which are lost from DCs by enhanced secretion. As these effects on DCs can be mimicked by chemical actin disruption, our results propose that Cdc42 control of actin dynamics keeps DCs in an immature state, and cessation of Cdc42 activity during DC maturation facilitates secretion as well as rapid up-regulation of intracellular molecules to the cell surface.
    Full-text · Article · Nov 2015 · The Journal of Cell Biology
    • "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.
    No preview · Article · Aug 2015 · Developmental Cell
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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.
    Full-text · Article · May 2015 · Cell Reports
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