Targeting the actin-binding protein VASP to late endosomes induces the formation of giant actin aggregates

Schmauch, Christian; Claussner, Susan; Zöltzer, H; Maniak, Markus

doi:10.1016/j.ejcb.2009.02.185

Cited by 9 publications

(11 citation statements)

References 42 publications

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“…It has been postulated that the presence of protein aggregates might affect cell function not only by means of its steric effects but also by sequestering other proteins that might be attracted to the aggregate by specific interaction with other existing proteins. Recently the formation of actin inclusions in Dictyostelium cells by mistargeting VASP, an actin-binding protein, to endosomes 23 has been described. These actin aggregates sequester other actinbinding proteins and endosomal proteins promoting their disappearance from the cytosol.…”

Section: Discussionmentioning

confidence: 99%

“…19,20 Regarding the study of protein aggregates, Dictyostelium has been used to address the formation of Hirano bodies, actin-rich inclusions frequently associated with neurodegenerative diseases. [21][22][23] Interestingly, Hirano bodies can be cleared by autophagy in Dictyostelium. 24 Dictyostelium cells feed on bacteria by phagocytosis and remain in the form of individual cells while bacteria are present.…”

Section: Vmp1 Localization and Its Role In Starvation And Autophagic mentioning

confidence: 99%

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Autophagy dysfunction and ubiquitin-positive protein aggregates in Dictyostelium cells lacking Vmp1

Calvo‐Garrido¹,

Escalante²

2010

Autophagy

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Ubiquitin-positive protein aggregates are a hallmark of many degenerative diseases. Their presence can be induced by dysfunction in protein degradation pathways such as proteasome and autophagy. We now report several lines of evidence suggesting a defect in autophagy in Dictyostelium cells lacking Vmp1 (vacuole membrane protein 1), an endoplasmic reticulum (ER)-resident protein involved in pathological processes such as cancer and pancreatitis. vmp1- null cells are unable to survive starvation or undergo autophagic cell death under the appropriate inductive signals. Moreover, confocal studies using the autophagy marker Atg8 and previous transmission electron microscopy analysis showed defects in autophagosome formation. Although Vmp1 is localized in the ER, we found colocalization with Atg8 suggesting a contribution of both Vmp1 and ER in autophagosome biogenesis or maturation. Interestingly, vmp1- mutant cells showed accumulation of huge ubiquitin-positive protein aggregates containing the autophagy marker GFP-Atg8 and the putative Dictyostelium p62 homologue as described in many degenerative human diseases. The analysis of other Dictyostelium autophagic mutants (atg1-, atg5-, atg6-, atg7- and atg8-) showed a correlation in the severity of their corresponding phenotypes and the presence of ubiquitin-positive protein aggregates suggesting that the deleterious effects associated with development of these aggregates might contribute to the complex phenotypes observed in autophagy deficient mutants. Our results suggest that Vmp1 is required for the clearance of these ubiquitinated protein aggregates through autophagy and highlight a potential role for Vmp1 in protein-aggregation diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Vmp1 Localization and Its Role In Starvation And Autophagic mentioning

confidence: 99%

Autophagy dysfunction and ubiquitin-positive protein aggregates in Dictyostelium cells lacking Vmp1

Calvo‐Garrido¹,

Escalante²

2010

Autophagy

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“…These actin aggregates are reminiscent of Hirano bodies that are often present in neurodegenerative diseases and, in Dictyostelium, are found to sequester other actin-binding proteins and endosomal proteins, promoting their disappearance from the cytoplasm. 115 These Hirano body-like aggregates can also be induced in Dictyostelium by the overexpression of a truncated form of a 34 kDa actin-binding protein. 116 A recent report shows that both autophagy and the proteasome pathway contribute to the degradation of Hirano bodies in Dictyostelium.…”

Section: Dictyostelium Autophagy Mutants Are Affected In Developmentmentioning

confidence: 99%

Autophagy in Dictyostelium: Genes and pathways, cell death and infection

Calvo‐Garrido¹,

Carilla-Latorre²,

Kubohara³

et al. 2010

Autophagy

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“…However, jasplakinolide lacks cross-linking activity, suggesting that cross-linking of actin filaments is an essential element in the formation of paracrystalline order in Hirano bodies. Overexpression of VASP (vasodilator-stimulated phosphoprotein) tethered to endosomes in Dictyostelium produced large actin aggregates (51). VASP contains 1 actin-binding domain but forms tetramers in solution and can cross-link actin filaments.…”

Section: Discussionmentioning

confidence: 99%