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Free keywords:
POLARIZED EPITHELIAL-CELLS; MANNOSE 6-PHOSPHATE RECEPTORS; LUMINAL ER
PROTEINS; CARBOXYPEPTIDASE-E; PLASMA-MEMBRANE; GRANULE BIOGENESIS;
ENDOPLASMIC-RETICULUM; VACUOLAR HYDROLASES; SECRETOGRANIN-III; REGULATED
PATHWAYCa2+; TGN; protein sorting; secretory cargo;
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 prelysosomes 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 Ca2+ ATPase, SPCA1 (secretory pathway calcium ATPase 1), and the luminal 45 kDa Ca2+-binding protein, Cab45, for successful sorting of a subset of proteins at the TGN. We review progress in understanding these processes.