Anti-p47-UBX antibody fragments disrupt the Golgi structure
by
inhibiting its post-mitotic reassembly process. (a) Representative
immunofluorescence images of HeLa cells transfected with HA-tagged
anti-p47-UBX antibody fragments for 24 h and stained with an antibody
to Golgi marker GRASP55. Scale bar, 10 μm. (b–d) Quantification
of GRASP55 for the percentage of cells with fragmented Golgi (b),
number of Golgi items per cell (c), and the Golgi area per cell (d).
Data are shown as mean ± SEM from N = 3 independent
experiments. (e) Representative transmission electron microscopy images
of RLG, MGF (RLG treated with mitotic cytosol), and reassembled samples
(MGF treated with interphase cytosol). In brief, RLG membranes were
fragmented by treatment with mitotic HeLa cytosol, and MGFs were reisolated
and incubated with interphase cytosol alone or in the presence of
recombinant anti-p47-UBX scFvs. Scale bar, 500 nm. (f) Quantification
of the cisternal regrowth in (e). Results are shown as the mean percentage
of membranes in cisternae ±SEM, where 0% represents cisternal
regrowth in MGF (10.8 ± 1.7% of membranes in cisternae) and 100%
represents cisternal regrowth of MGFs incubated with interphase cytosol
alone (56.7 ± 1.1% of membranes in cisternae). Statistical analyses
were performed using two-tailed Student’s t-test. *p < 0.05; **p < 0.01;
***p < 0.001; and n.s., no significance. (g) Scheme
showing antibody fragment inhibitors of p97/p47 PPI-inhibiting Golgi
reassembly.