Elucidation of three-dimensional ultrastructure of Hirano bodies by the quick-freeze, deep-etch and replica method

Izumiyama, Naotaka; Ohtsubo, Kohichiro; Tachikawa, T; Nakamura, Hiroaki

doi:10.1007/bf00305865

Cited by 19 publications

(13 citation statements)

References 22 publications

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“…In cultured cells, formation of model Hirano bodies occurs by aggregation of smaller structures into larger ordered aggregates [22,37]. The accumulation of smaller ordered structures into a single aggregate initially gives rise to a fingerprint appearance in our culture model [22], which corresponds in appearance to fingerprint inclusions described previously [38]. We also observed smaller Hirano bodies (~1 μm) in this mouse model (Figure 6).…”

Section: Discussionsupporting

confidence: 74%

Transgenic mouse model for the formation of Hirano bodies

Furukawa

Stramiello

et al. 2011

BMC Neurosci

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BackgroundHirano bodies are actin-rich cytoplasmic inclusions found predominantly in the brain in association with a variety of conditions including aging and Alzheimer's disease. The function of Hirano bodies in normal aging and in progression of disease has not been extensively investigated due to a lack of experimental model systems. We have developed a transgenic mouse model by expression of a gain-of-function actin cross-linking protein mutant.ResultsWe used the Cre/loxP system to permit tissue specific expression of Hirano bodies, and employed the murine Thy 1 promoter to drive expression of Cre recombinase in the brain. Hirano bodies were observed in the cerebral cortex and hippocampus of homozygous double transgenic 6 month old mice containing Cre. The Hirano bodies were eosinophilic rods, and also exhibited the paracrystalline F-actin filament organization that is characteristic of these inclusions. Mice with Hirano bodies appear healthy and fertile, but exhibited some alterations in both short-term and long-term synaptic plasticity, including paired-pulse depression rather than facilitation, and decreased magnitude of early LTP.ConclusionsHirano bodies are not lethal and appear to have little or no effect on histology and tissue organization. Hirano bodies do modulate synaptic plasticity and exert clearly discernable effects on LTP and paired-pulse paradigms. This model system will allow us to investigate the impact of Hirano bodies in vivo, the pathways for formation and degradation of Hirano bodies, and whether Hirano bodies promote or modulate development of pathology and disease progression.

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Section: Discussionsupporting

confidence: 74%

Transgenic mouse model for the formation of Hirano bodies

Furukawa

Stramiello

et al. 2011

BMC Neurosci

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“…4 and 5). The Hirano bodies induced by the expression of the 34-kDa ⌬EF1 protein are similar to the Hirano bodies seen in autopsy samples of brain tissue on the basis of the following criteria: (i) the Hirano bodies are enriched for actin and actin binding proteins (19,22,25,27,39,61); (ii) the structures are highly ordered and present elliptical cross-sections that are rod or disk shaped, depending on the overall length (24,25); (iii) the appearance varies with the plane of section or tilt of the stage due to the paracrystalline order of the structure (62,69); (iv) the inclusions frequently reveal juxtaposition of ordered and disordered regions (53,62); and (v) the structures contain strata of intersecting or interwoven parallel filament arrays (62). Hirano bodies are distinct from actin-cofilin rods, which are needlelike structures composed of a single large bundle of longitudinally oriented actin filaments that can form either in the nucleus or in the cytoplasm.…”

Section: Discussionmentioning

confidence: 99%

Formation of Hirano Bodies Induced by Expression of an Actin Cross-Linking Protein with a Gain-of-Function Mutation

et al. 2003

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Hirano bodies are paracrystalline actin filament-containing structures reported to be associated with a variety of neurodegenerative diseases. However, the biological function of Hirano bodies remains poorly understood, since nearly all prior studies of these structures were done with postmortem samples of tissue. In the present study, we generated a full-length form of a Dictyostelium 34-kDa actin cross-linking protein with point mutations in the first putative EF hand, termed 34-kDa ⌬EF1. The 34-kDa ⌬EF1 protein binds calcium normally but has activated actin binding that is unregulated by calcium. The expression of the 34-kDa ⌬EF1 protein in Dictyostelium induces the formation of Hirano bodies, as assessed by both fluorescence microscopy and transmission electron microscopy. Dictyostelium cells bearing Hirano bodies grow normally, indicating that Hirano bodies are not associated with cell death and are not deleterious to cell growth. Moreover, the expression of the 34-kDa ⌬EF1 protein rescues the phenotypes of cells lacking the 34-kDa protein and cells lacking both the 34-kDa protein and ␣-actinin. Finally, the expression of the 34-kDa ⌬EF1 protein also initiates the formation of Hirano bodies in cultured mouse fibroblasts. These results show that the failure to regulate the activity and/or affinity of an actin cross-linking protein can provide a signal for the formation of Hirano bodies. More generally, the formation of Hirano bodies is a cellular response to or a consequence of aberrant function of the actin cytoskeleton.

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“…Importantly, actin rods and Hirano bodies are actin paracrystallike intracellular structures (Hirano et al, 1968;Izumiyama et al, 1991;Hirano, 1994;Minamide et al, 2000). However, an ordered structure is usually not present in F-actin aggresomes, although it is occasionally seen in some areas, which by size and morphology most likely correspond to parallel arrays of microfilaments or actin bundles.…”

Section: The Single Large F-actin Aggregate Produced By Jasplakinolimentioning

confidence: 99%

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

Lázaro‐Diéguez

Aguado

Mato

et al. 2008

Journal of Cell Science

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In this study, we report the formation of several cytoplasmic inclusion bodies composed of filamentous actin (F-actin) and generated by experimental treatments using depolymerizing or stabilizing actin toxins in neuronal and non-neuronal mammalian cell lines. The actin-stabilizing toxin jasplakinolide (Jpk) induced, in a microtubule-dependent manner, a single, large F-actin aggregate, which contained β- and γ-actin, ADF/cofilin, cortactin, and the actin nucleator Arp2/3. This aggregate was tightly associated with the Golgi complex and mitochondria, and was surrounded by vimentin intermediate filaments, microtubules and MAP4. Therefore, the Jpk-induced single, large F-actin aggregate fits the established criteria for being considered an aggresome. Lysosomes and/or autophagic vacuoles, proteasomes and microtubules were found to directly participate in the dissolution of this F-actin aggresome. Finally, the model reported here is simple, highly reproducible and reversible, and it provides an opportunity to test pharmacological agents that interfere with the formation, maintenance and/or disappearance of F-actin-enriched pathological inclusion bodies.

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Elucidation of three-dimensional ultrastructure of Hirano bodies by the quick-freeze, deep-etch and replica method

Cited by 19 publications

References 22 publications

Transgenic mouse model for the formation of Hirano bodies

Transgenic mouse model for the formation of Hirano bodies

Formation of Hirano Bodies Induced by Expression of an Actin Cross-Linking Protein with a Gain-of-Function Mutation

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

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