Protein secretion: Sorting sweet sorting

How are proteins sorted to different destinations in eukaryotic cells? Until recently, it was generally thought that the constitutive flow of proteins to the cell surface occurs by default, and that proteins simply accumulate carbohydrate modifications as they pass sequentially through each compartment along the secretory pathway [1]. This hypothesis was supported by studies showing that inhibition of Nlinked glycosylation by drugs or genetic defects in certain carbohydrate modification enzymes did not stop protein secretion [1–3]. It is becoming evident, however, that cytosolic and lumenal machinery play a crucial role in determining protein flow through the secretory pathway [4]. The finding that membrane-spanning lectins resident in compartments along this route appear to regulate protein transport between successive compartments is an important new development [5–9].