Constitutive protein secretion from the trans-Golgi network to the plasma membrane

Constitutive secretion is used to deliver newly synthesized proteins to the cell surface and to the extracellular milieu. The trans-Golgi network is a key station along this route that mediates sorting of proteins into distinct transport pathways, aided in part by clathrin and adaptor proteins. Subsequent movement of proteins to the plasma membrane can occur either directly or via the endocytic pathway. Moreover, multiple, parallel pathways from the trans-Golgi network to the plasma membrane appear to exist, not only in complex, polarized cells such as epithelial cells and neurons, but also in relatively simple cells such as fibroblasts. In addition to typical secretory vesicles, these pathways involve both small, pleiomorphic transport containers and relatively large tubular-saccular carriers that travel along cytoskeletal tracks. While production and movement of these membranous structures are typically described as constitutive, recent studies have revealed that these key steps in secretion are tightly regulated by Ras-superfamily GTPases, members of the protein kinase D family and tethering complexes such as the exocyst.