B. Jungnickel et Ta. Rapoport, DIDS (4,4'-DIISOTHIOCYANATOSTILBENE-2,2'-DISULFONIC ACID) INHIBITS ANEARLY STEP OF PROTEIN TRANSLOCATION ACROSS THE MAMMALIAN ER MEMBRANE, FEBS letters, 329(3), 1993, pp. 268-272
Protein translocation across the endoplasmic reticulum (ER) membrane o
f yeast can be inhibited by agents believed to specifically affect the
transport of ATP through the membrane (Mayinger, P. and Meyer, D.I. (
1993) EMBOJ. 12,659-666), suggesting the involvement of a translocatio
n component in the lumen of the ER that binds ATP. We demonstrate that
one of the inhibitors, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic
acid (DIDS), also affects the translocation of proteins into mammalian
microsomes. Translocation is blocked at the point of transfer of the
nascent chain from the signal recognition particle (SRP) into the ER-m
embrane. We also confirm that photoaffinity-labelling of microsomes wi
th 8-azido-ATP inhibits the same early step of protein translocation.
Since this step is reported to not require ATP, these results raise th
e possibility that, in both cases, factor(s) other than ATP-binding co
mponents of the translocation machinery are perturbed.