Characterization of the L531A/V532A CHT (LV-AA) mutant in transiently
transfected cell lines. (A) Comparison of cell surface residence among
CHT, L531A, V532A, and LV-AA CHT in transiently transfected COS-7
cells. Following cell surface biotinylation, total (T) or surface
(S) fractions or the wild type and each mutant CHT were examined.
The total fractions represent 10% of the input into the biotinylated
protein extractions. (B) Saturation kinetic analysis of CHT LV-AA
compared to WT CHT was performed in transiently transfected COS-7
cells. CHT LV-AA has a significant increase in activity compared to
WT CHT (two way ANOVA interaction P-value <0.001
to 0.003). (C) The measured Vmax was 0.0676
± 00841 pmol choline/min·mg for WT CHT versus 0.463 ±
00.119 pmol choline/min·mg for CHT LV-AA (p =
0.0006, n = 5, two way ANOVA). The KM was not significantly altered by the mutation (data
not shown), 10.58 ± 4.287 μM for WT CHT versus 7.484 ±
2.581 μM for CHT LV-AA (Student’s t test).
(D) Biotinylation-stripping endocytosis assay by treatment with MesNa
after incubation at 37 °C for 5–15 min shows a greater
level CHT LV-AA maintained on the cell surface than WT CHT. (E) Quantification
of internalization at 5 min finds an impact of the LV-AA CHT mutation
as a reduction in the percent internalized protein compared to the
WT CHT (p = 0.03, n = 3, Student’s t-test).