The ADP-ribosylation factor GTPase-activating protein Glo3p is involved inER retrieval

Retrograde transport of proteins from the Golgi to the endoplasmic reticulu m (ER) has been the subject of some interest in the recent past. Here a new thermosensitive yeast mutant defective in retrieval of dilysine-tagged pro teins from the Golgi back to the endoplasmic reticulum was characterized. T he ret4-1 mutant also exhibited a selective defect in forward ER-to-Golgi t ransport of some secreted proteins at the nonpermissive temperature. The co rresponding RET4 gene was found to encode Glo3p, a GTPase-activating protei n (GAP) specific for ADP-ribosylation factor (ARF). In vitro, the Glo3 ther mosensitive mutant showed a reduced ARF1-GAP activity. The Glo3 protein bel ongs to a family of zinc finger proteins that may include additional ARF-GA Ps. Gene deletion experiments of other family members showed that only GLO3 deletion resulted in impaired retrieval of dilysine-tagged proteins back t o the ER. These results demonstrate that Glo3p is the main ARF-GAP specific ally involved in ER retrieval.