Non-overlapping activities of ADF and cofilin-1 during the migration of metastatic breast tumor cells

Tahtamouni, Lubna H.; Shaw, Alisa E.; Hasan, Maram; Yasin, Salem R.; Bamburg, James R.

doi:10.1186/1471-2121-14-45

Cited by 47 publications

(49 citation statements)

References 72 publications

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“…Many cellular proteins influence the dynamics of actin assembly, but the ADF (aka destrin)/cofilin family of proteins are particularly interesting because of their regulation and diverse functions, including maintaining cellular homeostasis [reviewed in Bernstein and Bamburg, 2010]. Although ADF and cofilin-1 have subtle differences in their quantitative interactions with actin in vitro [Chen et al, 2004;Pope et al, 2004] and in vivo [Tahtamouni et al, 2013;Wolf et al, 2015], they can substitute for each other qualitatively in some but not all cellular functions [e.g. Hotulainen et al, 2005;Wiggan et al, 2012].…”

Section: Body Actin Dynamics and Development Of Cofilin Pathologymentioning

confidence: 99%

Actin dynamics and cofilin‐actin rods in alzheimer disease

2016

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Cytoskeletal abnormalities and synaptic loss, typical of both familial and sporadic Alzheimer disease (AD), are induced by diverse stresses such as neuroinflammation, oxidative stress, and energetic stress, each of which may be initiated or enhanced by proinflammatory cytokines or amyloid-β (Aβ) peptides. Extracellular Aβ-containing plaques and intracellular phospho-tau-containing neurofibrillary tangles are postmortem pathologies required to confirm AD and have been the focus of most studies. However, AD brain, but not normal brain, also have increased levels of cytoplasmic rod-shaped bundles of filaments composed of ADF/cofilin-actin in a 1:1 complex (rods). Cofilin, the major ADF/cofilin isoform in mammalian neurons, severs actin filaments at low cofilin/actin ratios and stabilizes filaments at high cofilin/actin ratios. It binds cooperatively to ADP-actin subunits in F-actin. Cofilin is activated by dephosphorylation and may be oxidized in stressed neurons to form disulfide-linked dimers, required for bundling cofilin-actin filaments into stable rods. Rods form within neurites causing synaptic dysfunction by sequestering cofilin, disrupting normal actin dynamics, blocking transport, and exacerbating mitochondrial membrane potential loss. Aβ and proinflammatory cytokines induce rods through a cellular prion protein-dependent activation of NADPH oxidase and production of reactive oxygen species. Here we review recent advances in our understanding of cofilin biochemistry, rod formation, and the development of cognitive deficits. We will then discuss rod formation as a molecular pathway for synapse loss that may be common between all three prominent current AD hypotheses, thus making rods an attractive therapeutic target.

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Section: Body Actin Dynamics and Development Of Cofilin Pathologymentioning

confidence: 99%

Actin dynamics and cofilin‐actin rods in alzheimer disease

2016

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“…Additional genetic insights into ADF/Cofilin isoform function have come from silencing studies in cultured cells. Several groups have shown that depletion of Cof1 impairs directed cell migration, and that these defects can only be rescued by Cof1 and not ADF [10, 11, 17, 18]. Collectively, these observations indicate that while the three ADF/Cofilins may have some overlapping functions, they also perform unique roles in vivo.…”

Section: Introductionmentioning

confidence: 99%

TIRF microscopy analysis of human Cof1, Cof2, and ADF effects on actin filament severing and turnover

Chin

Jansen

Goode

2016

Journal of Molecular Biology

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Dynamic remodeling and turnover of cellular actin networks requires actin filament severing by Actin-Depolymerizing Factor (ADF)/Cofilin proteins. Mammals express three different ADF/Cofilins (Cof1, Cof2, and ADF), and genetic studies suggest that in vivo they perform both overlapping and unique functions. To gain mechanistic insights into their different roles, we directly compared their G-actin and F-actin binding affinities, and quantified the actin filament severing activities of human Cof1, Cof2, and ADF using in vitro TIRF microscopy. All three ADF/Cofilins had similar affinities for G-actin and F-actin. However, Cof2 and ADF severed filaments much more efficiently than Cof1 at both lower and higher concentrations and using either muscle or platelet actin. Further, Cof2 and ADF were more effective than Cof1 in promoting ‘enhanced disassembly’ when combined with actin disassembly co-factors Coronin-1B and Actin-Interacting Protein 1 (AIP1), and these differences were observed on both preformed and actively growing filaments. To probe the mechanism underlying these differences, we used multi-wavelength TIRF microscopy to directly observe Cy3-Cof1 and Cy3-Cof2 interacting with actin filaments in real time during severing. Cof1 and Cof2 each bound to filaments with similar kinetics, yet Cof2 induced severing much more rapidly than Cof1, decreasing the time interval between initial binding on a filament and severing at the same location. These differences in ADF/Cofilin activities and mechanisms may be used in cells to tune filament turnover rates, which can vary widely for different actin structures.

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“…This makes cofilins pivotal regulators of actin-based membrane protrusion and cell locomotion (reviewed in Bravo-Cordero et al, 2013). However, despite their similarity, it is still under debate whether each isoform fulfils unique roles at the cell periphery; a recent study suggests that they do because ADF or CFL1 depletion leads to characteristic differences in cell migration, focal adhesion turnover and formation of aberrant actin structures for each isoform (Tahtamouni et al, 2013).…”

Section: Localizationmentioning

confidence: 99%

Cellular functions of the ADF/cofilin family at a glance

Kanellos

Frame

2016

Journal of Cell Science

210

189

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The actin depolymerizing factor (ADF)/cofilin family comprises small actin-binding proteins with crucial roles in development, tissue homeostasis and disease. They are best known for their roles in regulating actin dynamics by promoting actin treadmilling and thereby driving membrane protrusion and cell motility. However, recent discoveries have increased our understanding of the functions of these proteins beyond their well-characterized roles. This Cell Science at a Glance article and the accompanying poster serve as an introduction to the diverse roles of the ADF/cofilin family in cells.The first part of the article summarizes their actions in actin treadmilling and the main mechanisms for their intracellular regulation; the second part aims to provide an outline of the emerging cellular roles attributed to the ADF/cofilin family, besides their actions in actin turnover. The latter part discusses an array of diverse processes, which include regulation of intracellular contractility, maintenance of nuclear integrity, transcriptional regulation, nuclear actin monomer transfer, apoptosis and lipid metabolism. Some of these could, of course, be indirect consequences of actin treadmilling functions, and this is discussed.

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Non-overlapping activities of ADF and cofilin-1 during the migration of metastatic breast tumor cells

Cited by 47 publications

References 72 publications

Actin dynamics and cofilin‐actin rods in alzheimer disease

Actin dynamics and cofilin‐actin rods in alzheimer disease

TIRF microscopy analysis of human Cof1, Cof2, and ADF effects on actin filament severing and turnover

Cellular functions of the ADF/cofilin family at a glance

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