S-Palmitoylation Sorts Membrane Cargo for Anterograde Transport in the Golgi

• DOI: 10.1016/j.devcel.2018.10.024
• Publication Date: 2018-11-19T15:39:00Z
• Authors: Andreas M. Ernst; Saad A. Syed; Omar Zaki; Francesca Bottanelli; Hong Zheng; Moritz Hacke; Zhiqun Xi; Felix Rivera-Molina; Morven Graham; Aleksander A. Rebane; Patrik Björkholm; David Baddeley; Derek Toomre; Frederic Pincet; James E. Rothman
• Keywords: 0301 basic medicine; Trafficking; [PHYS.PHYS]Physics [physics]/Physics [physics]; Lipoylation; Golgi Apparatus; Biological Transport; Intracellular Membranes; Endoplasmic Reticulum; Protein Transport; 03 medical and health sciences; S-palmitoylation; trafficking; cargo sorting; Golgi; Humans; DHHC; Cells, Cultured

While retrograde cargo selection in the Golgi is known to depend on specific signals, it is unknown whether anterograde cargo is sorted, and anterograde signals have not been identified. We suggest here that S-palmitoylation of anterograde cargo at the Golgi membrane interface is an anterograde signal and that it results in concentration in curved regions at the Golgi rims by simple physical chemistry. The rate of transport across the Golgi of two S-palmitoylated membrane proteins is controlled by S-palmitoylation. The bulk of S-palmitoylated proteins in the Golgi behave analogously, as revealed by click chemistry-based fluorescence and electron microscopy. These palmitoylated cargos concentrate in the most highly curved regions of the Golgi membranes, including the fenestrated perimeters of cisternae and associated vesicles. A palmitoylated transmembrane domain behaves similarly in model systems.