YKT6P, A PRENYLATED SNARE ESSENTIAL FOR ENDOPLASMIC-RETICULUM GOLGI TRANSPORT

Vesicular transport between secretory compartments requires specific r ecognition molecules called SNAREs, Here we report the identification of three putative SNAREs, p14 (Sft1p), p28 (Qos1p), and a detailed cha racterization of p26 (Ykt6p). All three were originally isolated as in teracting partners of the cis Golgi target membrane-associated SNARE S ed5p, when Sec18p (yeast NSF) was inactivated, YKT6 is an essential ge ne that codes for a novel vesicle-associated SNARE functioning at the endoplasmic reticulum-Golgi transport step in the yeast secretory path way, Depletion of Ykt6p results in the accumulation of the pi precurso r (endoplasmic reticulum form) of the vacuolar enzyme carboxypeptidase Y and morphological abnormalities consistent with a defect in secreti on, Membrane localization of Ykt6p is essential fur protein function a nd is normally mediated by isoprenylation, However, replacement of the isoprenylation motif with a bona fide transmembrane anchor results in a functional protein confirming that membrane localization, but not i soprenylation pel se, is required for function, Ykt6p and its homologu es are highly conserved from yeast to human as demonstrated by the fun ctional complementation of the lass of Ykt6p by its human counterpart, This is the first example of a human SNARE protein functionally repla cing a yeast SNARE, This observation implies that the specific details of the vesicle targeting code, like the genetic code, are conserved i n evolution.