Cargo sorting at the trans-Golgi network at a glance

Abstract

The Golgi functions principally in the biogenesis and trafficking of glycoproteins and lipids. It is compartmentalized into multiple flattened adherent membrane sacs termed cisternae, which each contain a distinct repertoire of resident proteins, principally enzymes that modify newly synthesized proteins and lipids sequentially as they traffic through the stack of Golgi cisternae. Upon reaching the final compartments of the Golgi, the trans cisterna and trans-Golgi network (TGN), processed glycoproteins and lipids are packaged into coated and non-coated transport carriers derived from the trans Golgi and TGN. The cargoes of clathrin-coated vesicles are chiefly residents of endo-lysosomal organelles, while uncoated carriers ferry cargo to the cell surface. There are outstanding questions regarding the mechanisms of protein and lipid sorting within the Golgi for export to different organelles. Nonetheless, conceptual advances have begun to define the key molecular features of cargo clients and the mechanisms underlying their sorting into distinct export pathways, which we have collated in this Cell Science at a Glance article and the accompanying poster.

Liquid–liquid phase separation facilitates the biogenesis of secretory storage granules

“…Secretory proteins are synthesized, glycosylated, folded, and quality checked in the endoplasmic reticulum (ER) lumen before being loaded onto carriers for transport to the Golgi apparatus ( Brandizzi and Barlowe, 2013 ; Dancourt and Barlowe, 2009 ; Miller and Barlowe, 2010 ). These secretory proteins travel across the Golgi stacks and are sorted at the trans-Golgi network (TGN; Ford et al, 2021 ). The TGN sorts and targets proteins to their destination through vesicular transport carriers ( Kienzle and von Blume, 2014 ; Ramazanov et al, 2021 ).…”

Sorting of secretory proteins at the trans-Golgi network by human TGN46

“…The accurate and timely export of cargo proteins is essential for the maintenance of cell and tissue homeostasis, and, accordingly, errors in this process can have severe physiological and pathophysiological consequences 6 . Despite the importance of this process, identification of the molecular machinery and the mechanisms of cargo sorting at the TGN remain largely elusive [7][8][9][10] . In mammalian cells, lysosomal hydrolases bearing a mannose 6-phosphate are sorted by the mannose 6-phosphate receptors into clathrincoated vesicles for their transport to the endo-lysosomal system 11,12 .…”

GOPC facilitates the sorting of syndecan-1 in polarized epithelial cells

“…The trans -Golgi network (TGN) is an integral protein and lipid sorting center and mediates the recognition, packaging, and targeting of cargoes for delivery to the plasma membrane or intracellular organelles. The heterogeneity of proteins and destinations inevitably requires multiple cargo recognition modules, signaling pathways, and the formation of coated and uncoated transport carriers at the TGN ( Ford et al. , 2021 ; Ramazanov et al.…”

“…, 2021 ). Amino acid sequence–based signals for basolateral sorting of proteins are slightly better defined: tyrosine- or dileucine-based sorting motifs present in the cytoplasmic tails of cargo proteins (YXXΦ or [DE]XXXL[LI] [where X is any amino acid and Φ is a bulky hydrophobic amino acid]) ( Tan and Gleeson, 2019 ; Ford et al. , 2021 ).…”