GPI anchors are widely represented among organisms and have several cellula
r functions. It has been proposed that in yeast there are two groups of GPI
proteins: plasma membrane-resident proteins, such as Gas1p or Yap3p, and c
ell wall-targeted proteins, such as Tir1p or ar-agglutinin. A model has bee
n proposed for the plasma membrane retention of proteins from the first gro
up because of a dibasic motif located just upstream of the GPI-anchoring si
gnal. The results we report here are not in agreement with such a model as
we show that constructs containing the C-terminal parts of Gas1p and Yap3p
are also targeted to the cell wall. We also detect the genuine Gas1p after
cell wall treatment with Quantazyme or Glucanex glycanases. In addition, we
show that the GPI-anchoring signal from the human placental alkaline phosp
hatase (PLAP) is not compatible with the yeast machinery unless the human t
ransamidase hGpi8p is co-expressed. In this condition, this human signal is
able to target a protein to the cell wall. Moreover, TIR1 proved to be a m
ulticopy suppressor of Delta gas1 mutation. The present findings suggest a
constitutive role for GPI anchors in yeast: the cell wall targeting of prot
eins.