Dynamics of an F-actin aggresome generated by the actin-stabilizing toxin jasplakinolide

Lázaro‐Diéguez, Francisco; Aguado, Carmen; Mato, Eugènia; Sanchez-Ruiz, Yovan; Esteban, Inmaculada; Alberch, Jordi; Knecht, Erwin; Egea, Gustavo

doi:10.1242/jcs.017665

Cited by 71 publications

(71 citation statements)

References 82 publications

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“…The actin-stabilizing toxin jasplakinolide induced, in a microtubuledependent manner, a single, large F-actin aggregate, which also contained cofilin (53). Although the RNP complexes found at the perinuclear region of MV-infected cells are apparently different from these aggresomes, the similar cell response may be responsible for inducing these structures.…”

Section: Discussionmentioning

confidence: 94%

Actin-Modulating Protein Cofilin Is Involved in the Formation of Measles Virus Ribonucleoprotein Complex at the Perinuclear Region

Koga

Sugita

Noda

et al. 2015

J Virol

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In measles virus (MV)-infected cells, the ribonucleoprotein (RNP) complex, comprised of the viral genome and the nucleocapsid (N) protein, phosphoprotein (P protein), and large protein, assembles at the perinuclear region and synthesizes viral RNAs. The cellular proteins involved in the formation of the RNP complex are largely unknown. In this report, we show that cofilin, an actin-modulating host protein, interacts with the MV N protein and aids in the formation of the RNP complex. Knockdown of cofilin using the short hairpin RNA reduces the formation of the RNP complex after MV infection and that of the RNP complex-like structure after plasmid-mediated expression of MV N and P proteins. A lower level of formation of the RNP complex results in the reduction of viral RNA synthesis. Cofilin phosphorylation on the serine residue at position 3, an enzymatically inactive form, is increased after MV infection and the phosphorylated form of cofilin is preferentially included in the complex. These results indicate that cofilin plays an important role in MV replication by increasing formation of the RNP complex and viral RNA synthesis. IMPORTANCE Many Measles is a highly contagious viral disease characterized by high fever, respiratory symptoms, conjunctivitis, and a macropapular rash. The patients exhibit immunosuppression, often resulting in secondary infections, the main cause of measles-associated mortality and morbidity. On rare occasions, measles virus (MV) persists in the central nervous system and causes subacute sclerosing panencephalitis with long incubation periods (1). Although mortality and morbidity have been greatly reduced thanks to worldwide vaccination efforts, the World Health Organization estimates that 145,700 people died of measles in 2013 (http://www .who.int/mediacentre/factsheets/fs286/en/).MV, a member of the genus Morbillivirus in the family Paramyxoviridae, possesses 6 genes coding for the nucleocapsid (N) protein, phosphoprotein (P protein), matrix (M) protein, and hemagglutinin (HA), fusion, and large proteins. The two envelope glycoproteins, the hemagglutinin and fusion proteins, mediate receptor binding and membrane fusion, respectively (1). Pathogenic MVs use as cellular receptors the signaling lymphocyte activation molecule (SLAM) (2, 3) and nectin 4 (4, 5), which are expressed on immune and epithelial cells, respectively. The N, P, and large proteins, together with the viral genome, constitute the ribonucleoprotein (RNP) complex, which is found at the perinuclear region in MV-infected cells (6-8) and functions as the RNAdependent RNA polymerase. The M protein is involved in virion assembly and the budding process (1).Besides the P protein, the MV P gene encodes two additional proteins, C and V (9, 10). The V mRNA is produced through the insertion of a single nontemplated guanine at the editing site of the P gene during the transcription. The V protein possesses 231 amino acid residues in the N terminus which are identical to those possessed by the P protein and 68 unique resid...

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Section: Discussionmentioning

confidence: 94%

Actin-Modulating Protein Cofilin Is Involved in the Formation of Measles Virus Ribonucleoprotein Complex at the Perinuclear Region

Koga

Sugita

Noda

et al. 2015

J Virol

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“…However, it is clear that some cells under certain circumstances form very stable actin aggregates. Examples of structures with little or no actin and ABP turnover include actin bodies in quiescent yeast cells (Sagot et al, 2006), large F-actin aggregates in Vero cells (Lazaro-Dieguez et al, 2008), and now, SI-induced actin foci in pollen tubes. Currently, there are no explanations for the formation or unusual dynamic properties of these structures.…”

Section: Discussionmentioning

confidence: 99%

“…The SI-Induced Punctate F-Actin Foci Are Resistant to Depolymerization F-actin bodies in quiescent yeast cells and F-actin aggregates in Vero cells, which appear somewhat similar to the SI-induced F-actin foci, are highly resistant to treatments with latrunculin (Sagot et al, 2006;Lazaro-Dieguez et al, 2008). Latrunculins bind to monomeric actin and inhibit polymerization, so they lead to the preferential disassembly of actin filaments and arrays that are undergoing rapid turnover.…”

Section: Temporal Formation Of the Si-induced F-actin Focimentioning

confidence: 98%

Actin-Binding Proteins Implicated in the Formation of the Punctate Actin Foci Stimulated by the Self-Incompatibility Response inPapaver

et al. 2010

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The actin cytoskeleton is a key target for signaling networks and plays a central role in translating signals into cellular responses in eukaryotic cells. Self-incompatibility (SI) is an important mechanism responsible for preventing self-fertilization. The SI system of Papaver rhoeas pollen involves a Ca 2+ -dependent signaling network, including massive actin depolymerization as one of the earliest cellular responses, followed by the formation of large actin foci. However, no analysis of these structures, which appear to be aggregates of filamentous (F-)actin based on phalloidin staining, has been carried out to date. Here, we characterize and quantify the formation of F-actin foci in incompatible Papaver pollen tubes over time. The F-actin foci increase in size over time, and we provide evidence that their formation requires actin polymerization. Once formed, these SI-induced structures are unusually stable, being resistant to treatments with latrunculin B. Furthermore, their formation is associated with changes in the intracellular localization of two actin-binding proteins, cyclase-associated protein and actin-depolymerizing factor. Two other regulators of actin dynamics, profilin and fimbrin, do not associate with the F-actin foci. This study provides, to our knowledge, the first insights into the actin-binding proteins and mechanisms involved in the formation of these intriguing structures, which appear to be actively formed during the SI response.

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“…Many aggresomes of proteins, such as mutant huntingtin (Q150Htt), filamentous actin (F-actin) and the ⌬F508 mutant of the cystic fibrosis transmembrane conductance regulator (⌬F508-CFTR), are known to be degraded by the autophagy-2694 Journal of Cell Science 124 (16) lysosome pathway (Iwata et al, 2005;Lázaro-Diéguez et al, 2008). Therefore, we examined whether the aggresomes and aggregates of STAT5A_⌬E18 were degraded by the autophagy-lysosome pathway.…”

Section: Aggresome Formation Of Stat5a_⌬e18mentioning

confidence: 99%

p62/SQSTM1 in autophagic clearance of a non-ubiquitylated substrate

Watanabe

Tanaka

2011

Journal of Cell Science

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SummaryProteolytic systems and the aggresome pathway contribute to preventing accumulation of cytotoxic aggregation-prone proteins. Although polyubiquitylation is usually required for degradation or aggresome formation, several substrates are processed independently of ubiquitin through a poorly understood mechanism. Here, we found that p62/SQSTM1, a multifunctional adaptor protein, was involved in the selective autophagic clearance of a non-ubiquitylated substrate, namely an aggregation-prone isoform of STAT5A (STAT5A_⌬E18). By using a cell line that stably expressed STAT5A_⌬E18, we investigated the properties of its aggregation and degradation. We found that STAT5A_⌬E18 formed non-ubiquitylated aggresomes and/or aggregates by impairment of proteasome functioning or autophagy. Transport of these aggregates to the perinuclear region was inhibited by trichostatin A or tubacin, inhibitors of histone deacetylase (HDAC), indicating that the non-ubiquitylated aggregates of STAT5A_⌬E18 were sequestered into aggresomes in an HDAC6-dependent manner. Moreover, p62 was bound to STAT5A_⌬E18 through its PB1 domain, and the oligomerization of p62 was required for this interaction. In p62-knockdown experiments, we found that p62 was required for autophagic clearance of STAT5A_⌬E18 but not for its aggregate formation, suggesting that the binding of p62 to non-ubiquitylated substrates might trigger their autophagic clearance.

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Dynamics of an F-actin aggresome generated by the actin-stabilizing toxin jasplakinolide

Cited by 71 publications

References 82 publications

Actin-Modulating Protein Cofilin Is Involved in the Formation of Measles Virus Ribonucleoprotein Complex at the Perinuclear Region

Actin-Modulating Protein Cofilin Is Involved in the Formation of Measles Virus Ribonucleoprotein Complex at the Perinuclear Region

Actin-Binding Proteins Implicated in the Formation of the Punctate Actin Foci Stimulated by the Self-Incompatibility Response inPapaver

p62/SQSTM1 in autophagic clearance of a non-ubiquitylated substrate

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