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: 36.46). 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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Available from: Christopher Pierre Toret, Aug 27, 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 · 10.37 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 · 5.33 Impact Factor
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    • "Although girdin was reported to be a component of a protein complex that included dynamin (Simpson et al, 2005), the role of girdin in CME has not been investigated. Also, our previous finding that girdin colocalizes with submembranous actin network (Enomoto et al, 2005), which possess critical roles in CME (Kaksonen et al, 2006), led to the idea of girdin's involvement in CME. "
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    ABSTRACT: In clathrin-mediated endocytosis (CME), specificity and selectivity for cargoes are thought to be tightly regulated by cargo-specific adaptors for distinct cellular functions. Here, we show that the actin-binding protein girdin is a regulator of cargo-selective CME. Girdin interacts with dynamin 2, a GTPase that excises endocytic vesicles from the plasma membrane, and functions as its GTPase-activating protein. Interestingly, girdin depletion leads to the defect in clathrin-coated pit formation in the center of cells. Also, we find that girdin differentially interacts with some cargoes, which competitively prevents girdin from interacting with dynamin 2 and confers the cargo selectivity for CME. Therefore, girdin regulates transferrin and E-cadherin endocytosis in the center of cells and their subsequent polarized intracellular localization, but has no effect on integrin and epidermal growth factor receptor endocytosis that occurs at the cell periphery. Our results reveal that girdin regulates selective CME via a mechanism involving dynamin 2, but not by operating as a cargo-specific adaptor.
    The EMBO Journal 07/2014; 33(18). DOI:10.15252/embj.201488289 · 10.75 Impact Factor
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