Trans-Golgi network sorting

Abstract

The trans-Golgi network (TGN) is a major secretory pathway sorting station that directs newly synthesized proteins to different subcellular destinations. The TGN also receives extracellular materials and recycled molecules from endocytic compartments. In this review, we summarize recent progress on understanding TGN structure and the dynamics of trafficking to and from this compartment. Protein sorting into different transport vesicles requires specific interactions between sorting motifs on the cargo molecules and vesicle coat components that recognize these motifs. Current understanding of the various targeting signals and vesicle coat components that are involved in TGN sorting are discussed, as well as the molecules that participate in retrieval to this compartment in both yeast and mammalian cells. Besides proteins, lipids and lipid-modifying enzymes also participate actively in the formation of secretory vesicles. The possible mechanisms of action of these lipid hydrolases and lipid kinases are discussed. Finally, we summarize the fundamentally different apical and basolateral cell surface delivery mechanisms and the current facts and hypotheses on protein sorting from the TGN into the regulated secretory pathway in neuroendocrine cells.

Age-Associated Changes in Histology and Gene-Expression Profile in the Rat Ventral Prostate

“…Vesicle transport and protein/membrane trafficking play major roles in trans-Golgi network function, lysosome biogenesis, endocytosis, and protein secretion. Our array analyses revealed a lower expression in the aged rats of a set of seven genes encoding proteins involved in vesicle coat formation (brain-type clathrin light chain b and clathrin-coat assembly protein-like) (Brodsky et al, 2001;Schmid, 1997), vesicle trafficking, and vesicle-mediated transport [Ras-related GTPbinding protein (Rab), Rab2, ADP-ribosylation factor-1 (ARF-1), ARF-like protein (ARL), and 14-3-3 protein epsilon] (Gu et al, 2001;Takei and Haucke, 2001). Clathrins, via interaction with adaptor complexes, are recruited to the cell membrane or to the trans-Golgi network, where they assemble into a lattice coat on vesicles (Grodsky et al, 1982;Schmid, 1997).…”

“…They also are implicated in Ras signaling pathways (Gelperin et al, 1995). Collectively, down-regulation of this set of genes in the aged VP will affect turnover of normal cellular proteins, disposal of abnormal proteins, internalization of cell-surface receptors, autophagy, release of exocytosed nutrients, inactivation of pathogens, and antigen processing (Brodsky et al, 2001;Gu et al, 2001;Schmid, 1997;Takei and Haucke, 2001). Little is known about the relationship between functional roles of these genes and prostatic function, except for a single report showing androgen regulation of clathrin light chains in LNCaP cells (Prescott and Tindall, 1998).…”

Transcytotic Efflux from Early Endosomes Is Dependent on Cholesterol and Glycosphingolipids in Polarized Hepatic Cells

“…In general, structural signals, such as amino acid sequences, conformations or modifications on the protein itself, are thought to specify the cellular destination. Several such signals required for basolateral PM targeting and/or localization have been identified, and generally they reside in the cytoplasmic tails of the proteins (reviewed in Ikonen and Simons, 1998;Gu et al, 2001;Tuma and Hubbard, 2001). Most of the signals contain either a tyrosine in the context of a short degenerate sequence or a dileucine motif.…”

Ordered assembly of the duplicating Golgi in Trypanosoma brucei

“…Several models have been put forward to explain transport through the Golgi, but in all cases COPI vesicles play a key role in mixing the transiting cargoes with resident enzymes in an ordered manner so that posttranslational modifications can be performed. Cargoes are then sorted in the late Golgi compartment, the trans-Golgi network (TGN), before onward delivery to their final destinations (1,2).…”