Article
Auto-regulation of Secretory Flux by Sensing and Responding to the Folded Cargo Protein Load in the Endoplasmic Reticulum
Fecha
2019Autor
Subramanian, Advait
Capalbo, Anita
Iyengar, Namrata Ravi
Rizzo, Riccardo
di Campli, Antonella
Di Martino, Rosaria
Lo Monte, Matteo
Beccari, Andrea R.
Yerudkar, Amol
del Vecchio, Carmen
Glielmo, Luigi
Turacchio, Gabriele
Pirozzi, Marinella
Kim, Sang Geon
Henklein, Petra
Cancino, Jorge
Parashuraman, Seetharaman
Diviani, Dario
Fanelli, Francesca
Sallese, Michele
Luini, Alberto
Institución
Resumen
Maintaining 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 G alpha 12 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.