TRANSMEMBRANE DOMAIN-DEPENDENT SORTING OF PROTEINS TO THE ER AND PLASMA-MEMBRANE IN YEAST

Sorting of membrane proteins between compartments of the secretory pat hway is mediated in part by their transmembrane domains (TMDs). In ani mal cells, TMD length is a major factor in Golgi retention, In yeast, the role of TMD signals is less clear; it has been proposed that membr ane proteins travel by default to the vacuole, and are prevented from doing so by cytoplasmic signals, We have investigated the targeting of the yeast endoplasmic reticulum (ER) t-SNARE Ufe1p. We show that the amino acid sequence of the Ufe1p TMD is important for both function an d ER targeting, and that the requirements for each are distinct. Targe ting is independent of Rer1p, the only candidate sorting receptor for TMD sequences currently known, Lengthening the Ufe1p TMD allows transp ort along the secretory pathway to the vacuole or plasma membrane, The choice between these destinations is determined by the length and com position of the TMD, but not by its precise sequence, A longer TMD is required to reach the plasma membrane in yeast than in animal cells, a nd shorter TMDs direct proteins to the vacuole, TMD-based sorting is t herefore a general feature of the yeast secretory pathway, but occurs by different mechanisms at different points.