Loss of AP-5 results in accumulation of aberrant endolysosomes: defining a new type of lysosomal storage disease
by Hirst J, Edgar JR, Esteves T, Darios F, Madeo M, Chang J, Roda RH, Dürr A, Anheim M, Gellera C, Li J, Züchner S, Mariotti C, Stevanin G,Blackstone C, Kruer MC, Robinson MS.
Ultrastructure of AP5Z1p.Q578* fibroblasts. (A) EM of patient-derived fibroblasts. Note the accumulation of morphologically defined endocytic structures filled with aberrant storage material typified by multiple exaggerated membrane whorls (filled arrow head), belts of striated material (double arrow), fingerprint bodies (arrow) and some intraluminal vesicles (open arrow head). These structures are predominantly surrounded by a single bilayer membrane, and there is clustering of endocytic structures marked by arrowheads with white outline (far left panel; EL, endolysosome). Scale bar = 500 nm. (B) Images were collected from 10 cells and the size of endocytic structures measured (96 for control_1 and 191 for the p.Q578* line); the individual data are shown for endolysosomes (Endolyso), endosomes (Endo) and lysosomes (Lyso) and combined together to show all endocytic structures. Note that no significant difference in the overall size of endocytic structures was revealed. (C) The number of different endocytic structures per unit area of cytoplasm was measured. Images were collected from 10 cells and the number of endocytic structures measured (96 for control_1 and 191 for the p.Q578* line). Note the increase in the number of endolysosomes per unit area of cytoplasm in the p.Q578* line. (D) Examples of AP5Z1p.Q578* fibroblasts showing the clustering of endolysosomes compared with its control. Scale bar = 1 µm.