Recent studies show that small trans-membrane proteins of approximate to 22
-24 kDa (the p24 family), which are grouped into 4 subfamilies by sequence
homology (p23, p24, p25 and p26), are involved in the early secretory pathw
ay, In this study, we have investigated the mutual requirements of ectopica
lly expressed members of the p24 family for targeting to their proper cellu
lar destination, We find that coexpression of p23 and p24 is both necessary
and sufficient for each protein to be transported to the cis-Golgi network
/Golgi complex. Proteins from other subfamilies did not substitute for eith
er p23 or p24, even after multiple coexpression, However, trafficking of th
e p23/p24 couple was facilitated by coexpression of proteins from other sub
-families. In addition, we find that the sequence resembling an endoplasmic
reticulum retrieval signal present in the cytoplasmic domain of p23 (but n
ot p24) is dispensable, In contrast, the conserved coiled-coil region in th
e lumenal domain is absolutely required in both p23 and p24 for proper targ
eting of the p23/p24 couple, These data demonstrate that p23 and p24 must i
nteract with each other to reach their destination, but that this strict re
quirement is combined with a mutual dependence amongst p24 proteins, We spe
culate that p24 proteins can form different oligomeric complexes, which con
tribute to confer specialized sorting/trafficking properties to membranes o
f the early secretory pathway, perhaps serving as membrane organizers.