Auto-regulation of Secretory Flux by Sensing and Responding to the Folded Cargo Protein Load in the Endoplasmic Reticulum

Publication date: 7 March 2019Source: Cell, Volume 176, Issue 6Author(s): Advait Subramanian, Anita Capalbo, Namrata Ravi Iyengar, Riccardo Rizzo, Antonella di Campli, Rosaria Di Martino, Matteo Lo Monte, Andrea R. Beccari, Amol Yerudkar, Carmen del Vecchio, Luigi Glielmo, Gabriele Turacchio, Marinella Pirozzi, Sang Geon Kim, Petra Henklein, Jorge Cancino, Seetharaman Parashuraman, Dario Diviani, Francesca Fanelli, Michele SalleseSummaryMaintaining the optimal performance of cell processes and organelles is the task of auto-regulatory systems. Here we describe an auto-regulatory device that helps to maintain homeostasis of the endoplasmic reticulum (ER) by adjusting the secretory flux to the cargo load. The cargo-recruiting subunit of the coatomer protein II (COPII) coat, Sec24, doubles as a sensor of folded cargo and, upon cargo binding, acts as a guanine nucleotide exchange factor to activate the signaling protein Gα12 at the ER exit sites (ERESs). This step, in turn, activates a complex signaling network that activates and coordinates the ER export machinery and attenuates proteins synthesis, thus preventing large fluctuations of folded and potentially active cargo that could be harmful to the cell or the organism. We call this mechanism AREX (autoregulation of ER export) and expect that its identification will aid our understanding of human physiology and diseases that develop from secretory dysfunction.Graphical Abstract

Source: Cell - March 8, 2019 Category: Cytology Source Type: research