Ultra-structural characterisation of endo/lysosomal compartments in wild type, <i>Cc2d1a</i>^-/-, <i>Cc2d1b</i>^-/- and <i>Vps4a</i>^+/-,<i>Vps4b</i>^+/- MEFs.

(A-A”) wild type, (B-B”) Cc2d1a-/- mutant, (C-C”) Cc2d1b-/- mutant and (D-D”) Vps4a+/-,Vps4b+/- double heterozygous MEFs. The comparison reveals that Cc2d1a-/- and Cc2d1b-/- contain endo/lysosomal organelles that are similar to wild type endo/lysosomal organelles in appearance. In contrast, the appearance of the organelles is dramatically changed in Vps4a+/-,Vps4b+/- double heterozygous cells. These cells contain massively enlarged MEs with a class E like phenotype. The MEs partially lose their normal round shape and contain many intraluminal vesicles or membrane layers (arrowheads). (E) Statistical analysis of the endo/lysosomal perimeter revealed that the organelles in Cc2d1a-/- and Vps4a+/-,Vps4b+/- MEFs are significantly enlarged compared to wild type cells. Data are mean ± SD values from 4 independent experiments (** p < 0.001). Arrows highlight individual endosomes. Scale bars are 5 μm (A-D) and 0.5 μm (A`-D`, A”-D”).