Effect of 2-fluoropalmitate, cerulenin and tunicamycin on
the palmitoylation and intracellular translocation of myelin proteolipid
DeJesus G, Bizzozero OA.
Department of Cell Biology and Physiology, University of New Mexico-School of
Medicine, Albuquerque, New Mexico 87131-5218, USA.
We have investigated the effect of documented protein palmitoylation inhibitors
on the fatty acylation and intracellular transport of myelin proteolipid protein
(PLP). To this end, brain slices from 20-day-old rats were incubated with either
[3H]palmitate or [3H]leucine in the presence or absence of various
concentrations of 2-fluoropalmitate (FP), cerulenin (CER), or tunicamycin (TM).
FP (> or = 10 microM) decreased the cellular uptake of [3H]palmitate and
consequently reduced the labeling of palmitoyl-CoA, glycerolipids and PLP. CER
(> or = 1 mM) reduced the palmitoylation of PLP with a concomitant decline in
protein thiols. Consistent with being a fatty acyl-CoA analogue, TM (> or = 200
microM) diminished the palmitoylation of PLP and lipids while increasing the
amount of [3H]palmitoyl-CoA. Although both CER and TM decreased protein
palmitoylation, only the latter affected the appearance of newly synthesized PLP
into myelin. Because TM, but not CER, also reduced the formation of lipids, it
is concluded that palmitoylation is not required for intracellular transport.
Finally, comparison of the effect of TM in brain slices and in a cell-free
system suggests that palmitoylation of PLP in whole cells may be an enzymatic