ER-export signals (p. 619)

The mechanism by which proteins are exported from the ER is controversial. Supporters of the `bulk flow' model contend that ER export is a default mechanism that does not require sorting signals in the cargo. Increasing evidence, however, indicates that at least some membrane proteins contain specific ER-export motifs. ERGIC-53 and p24, for example, contain a C-terminal FF motif necessary for efficient ER export. Hans-Peter Hauri and co-workers have used ERGIC-53 mutants to define the signals required for efficient ER export: a single F/Y residue at position -2; an II or LL sequence; or a single V residue at position -1. In fact, a ^-1V can even accelerate ER export of an otherwise slowly exported CD4 construct. These motifs are common in type I membrane proteins. Moreover, the authors demonstrate that they can bind to COPII components (the coat proteins involved in budding of vesicles from the ER) and exhibit different preferences for COPII isotypes. The motifs might thus represent a common ER-export signal that functions by interacting with COPII proteins.