Secretory cargo sorting at the trans-Golgi network

Abstract

Sorting of proteins for secretion from cells is crucial for normal physiology and the regulation of key cellular events. Although the sorting of lysosomal hydrolases at the trans-Golgi network (TGN) for delivery to pre-lysosomes is well characterized, the corresponding mechanism by which secreted proteins are sorted for plasma-membrane delivery remains poorly understood. Recent discoveries have revealed a novel sorting mechanism that requires the linkage between the cytoplasmic actin cytoskeleton to the membrane-anchored Ca(2+) ATPase, SPCA1 (secretory pathway calcium ATPase 1), and the luminal 45 kDa Ca(2+)-binding protein, Cab45, for successful sorting of a subset of proteins at the TGN. We review progress in understanding these processes.

Keywords: Ca(2+); TGN; protein sorting; secretory cargo.