A proteolytic cleavage assay to monitor autophagy in Dictyostelium discoideum

Dictyostelium discoideum is a good model of autophagy. However, the lack of autophagic flux techniques hinders the assessment of new mutants or drugs. One of these techniques, which has been used successfully in yeast and mammalian cells, but has not yet been described in Dictyostelium, is based on...

Descripción completa

Detalles Bibliográficos
Autores: Calvo-Garrido, Javier, Carilla-Latorre, Sergio, Mesquita, Ana, Escalante, Ricardo
Tipo de recurso: artículo
Fecha de publicación:2011
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/40098
Acceso en línea:http://hdl.handle.net/10261/40098
Access Level:acceso abierto
Palabra clave:Protein
Macroautophagy
Genes
Descripción
Sumario:Dictyostelium discoideum is a good model of autophagy. However, the lack of autophagic flux techniques hinders the assessment of new mutants or drugs. One of these techniques, which has been used successfully in yeast and mammalian cells, but has not yet been described in Dictyostelium, is based on the presence of proteolytic fragments derived from autophagic degradation of expressed fusion proteins. Lysosomotropic agents such as NH(4)Cl penetrate acidic compartments and raise their pH, thus allowing the accumulation and measurement of these cleaved fragments, which otherwise would be rapidly degraded. We have used this property to detect the presence of free GFP fragments derived from the fusion protein GFP-Tkt-1, a cytosolic marker. We demonstrate that this proteolytic event is dependent on autophagy and can be used to detect differences in the level of autophagic flux among different mutant strains. Moreover, treatment with NH(4)Cl also facilitates the assessment of autophagic flux by confocal microscopy using the marker RFP-GFP-Atg8.