Tail-anchored proteins are inserted into intracellular membranes via a C-te
rminal transmembrane domain. The topology of the protein is such that inser
tion must occur posttranslationally, since the insertion sequence is not av
ailable for membrane insertion until after translation of the tail-anchored
polypeptide is completed. Here, we show that the targeting information in
one such tail-anchored protein, translocase in the outer mitochondrial memb
rane 22, is contained in a short region flanking the transmembrane domain.
An equivalent region is sufficient to specify the localisation of Bcl2 and
SNARE proteins to the secretory membranes. We discuss the targeting process
for directing members of this protein family to the secretory and mitochon
drial membranes in vivo. (C) 1999 Federation of European Biochemical Societ
ies.