Article

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

ABSTRACT

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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    • "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. http://authors.elsevier.com/a/1Rb875Sx5gPQ4y
    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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