Altered composition and secretion of lysosome-derived compartments in Dictyostelium AP-3 mutant cells.
Genetic alteration of the adaptor protein (AP)-3 complex is responsible for the type 2 Hermansky-Pudlak syndrome, a lysosomal storage disease similar to the Chediak-Higashi syndrome (CHS). AP-3 presumably participates in the biogenesis of late endosomal compartments and may also be critical for the regulated secretion of lysosomes by specialized cells. Here, Dictyostelium discoideum cells defective for the mu3 subunit of the AP-3 complex were used and their phenotype analyzed. In mu3 mutant cells, endosomal maturation and lysosome secretion were markedly slower than that in wild-type cells. This phenotype is similar to that reported previously in lvsB mutant cells where the ortholog of the LYST gene, involved in CHS, is mutated. Detailed analysis revealed however significant differences between these two isogenic mutant cells: in lvsB mutant cells, the primary defect is an inefficient biogenesis of otherwise normal secretory lysosomes, while in mu3 mutant cells, the biogenesis and also the composition and the fusion properties of secretory lysosomes are affected. These results suggest that in D. discoideum, AP-3 controls both the efficiency and the specificity of postlysosome maturation, which represent two critical elements in the control of lysosome secretion.
Charette
Steve J
SJ
Centre de recherche en cancérologie de l'Université Laval, L'Hôtel-Dieu de Québec, Centre hospitalier universitaire de Québec, 9, rue McMahon, Québec, Canada G1R 2J6. steve.charette@bcm.ulaval.ca
Cosson
Pierre
P
D000199:Actins / Q000378:metabolism; D033963:Adaptor Protein Complex 3 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004023:Dictyostelium / Q000166:cytology* / Q000235:genetics / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology; D006801:Humans; D008247:Lysosomes / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D010641:Phenotype; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D033963:Adaptor Protein Complex 3; D021122:Protein Subunits