It is known that the proper function of the vacuolar H+-ATPase is inhibited
by bafilomycin A(1). In transfected cells the E5 protein interacts with th
e 16 kDa subunit of the vacuolar H+-ATPase. Thereby the pH gradient in endo
cytic structures is impaired. The present study demonstrates for the first
time that the inhibition of the vacuolar H+-ATPase in NIH3T3 cells with baf
ilomycin A(1) or by transfection of cells with the HPV-16 E5 oncogene leads
to a changed morphology and a reduced motility as shown by computer-assist
ed video recordings and image analysis. Bafilomycin A(1) potentiates the ef
fect of the E5 protein on cell motility and this cooperative effect indicat
es that the E5 protein and bafilomycin A(1) either target the vacuolar H+-A
TPase differently or that the E5 protein has additional targets in transfec
ted cells. Our data therefore show that proper function of-the vacuolar H+-
ATPase is needed for normal cell locomotion. (C) 1999 Elsevier Science B.V.
All rights reserved.