ERGIC-53 KKAA signal mediates endoplasmic reticulum retrieval in yeast

Studies on the ERGIC-53 KKAA signal have revealed a new mechanism for stati c retention of mammalian proteins in the endoplasmic reticulum (Andersson, H., Kappeler, F., Hauri, H. P. (1999): Protein targeting to endoplasmic ret iculum by dilysine signals involves direct retention in addition to retriev al, J. Biol. Chem. 274, 15080 - 15084). To test if this mechanism was conse rved in yeast, the ERGIC-53 KKAA signal was transferred on two different ye ast reporter proteins. Making use of a genetic assay, we demonstrate that t his signal induces COPI-dependent ER retrieval. ER retention of KKAA-tagged proteins was impaired in yeast mutants affected in COPI subunits. Furtherm ore, biochemical analysis of post-ER carbohydrate modifications detected on reporter proteins indicated that KKAA-tagged proteins recycle continuously within early compartments of the secretory pathway. Therefore in yeast, th e KKAA signal might only function as a classical dilysine ER retrieval sign al.