Auto-regulation of Secretory Flux by Sensing and Responding to the Folded Cargo Protein Load in the Endoplasmic Reticulum.
Biological Transport
COP-Coated Vesicles
/ metabolism
Cell Line
Coatomer Protein
/ metabolism
Endoplasmic Reticulum
/ metabolism
Endoplasmic Reticulum Stress
/ physiology
Female
GTP-Binding Protein alpha Subunits, G12-G13
/ metabolism
Golgi Apparatus
/ metabolism
Guanine Nucleotide Exchange Factors
/ physiology
HeLa Cells
Humans
Male
Protein Folding
Protein Transport
Proteostasis
/ physiology
Signal Transduction
Vesicular Transport Proteins
/ metabolism
AKAP
COPII
ER exit sites
ER export
PKA
auto-regulatory systems
folded cargo
homeostasis
membrane traffic
signaling
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
07 03 2019
07 03 2019
Historique:
received:
27
02
2018
revised:
30
08
2018
accepted:
23
01
2019
entrez:
9
3
2019
pubmed:
9
3
2019
medline:
7
1
2020
Statut:
ppublish
Résumé
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 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.
Identifiants
pubmed: 30849374
pii: S0092-8674(19)30098-4
doi: 10.1016/j.cell.2019.01.035
pii:
doi:
Substances chimiques
Coatomer Protein
0
Guanine Nucleotide Exchange Factors
0
SEC24A protein, human
0
Vesicular Transport Proteins
0
GTP-Binding Protein alpha Subunits, G12-G13
EC 3.6.5.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1461-1476.e23Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.