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Activation of Gαi at the Golgi by GIV/Girdin imposes finiteness in Arf1 signaling.
- Source :
-
Developmental cell [Dev Cell] 2015 Apr 20; Vol. 33 (2), pp. 189-203. Date of Electronic Publication: 2015 Apr 09. - Publication Year :
- 2015
-
Abstract
- A long-held tenet of heterotrimeric G protein signal transduction is that it is triggered by G protein-coupled receptors (GPCRs) at the PM. Here, we demonstrate that Gi is activated in the Golgi by GIV/Girdin, a non-receptor guanine-nucleotide exchange factor (GEF). GIV-dependent activation of Gi at the Golgi maintains the finiteness of the cyclical activation of ADP-ribosylation factor 1 (Arf1), a fundamental step in vesicle traffic in all eukaryotes. Several interactions with other major components of Golgi trafficking-e.g., active Arf1, its regulator, ArfGAP2/3, and the adaptor protein β-COP-enable GIV to coordinately regulate Arf1 signaling. When the GIV-Gαi pathway is selectively inhibited, levels of GTP-bound Arf1 are elevated and protein transport along the secretory pathway is delayed. These findings define a paradigm in non-canonical G protein signaling at the Golgi, which places GIV-GEF at the crossroads between signals gated by the trimeric G proteins and the Arf family of monomeric GTPases.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- ADP-Ribosylation Factors metabolism
Animals
Binding Sites genetics
COS Cells
Cell Line
Cell Membrane metabolism
Chlorocebus aethiops
Coatomer Protein metabolism
Enzyme Activation
GTP-Binding Protein alpha Subunits, Gi-Go antagonists & inhibitors
GTPase-Activating Proteins metabolism
HEK293 Cells
HeLa Cells
Humans
Microfilament Proteins antagonists & inhibitors
Protein Binding
Protein Structure, Tertiary
Protein Transport physiology
RNA Interference
RNA, Small Interfering
Signal Transduction
Vesicular Transport Proteins antagonists & inhibitors
ADP-Ribosylation Factor 1 metabolism
GTP-Binding Protein alpha Subunits, Gi-Go metabolism
Golgi Apparatus metabolism
Microfilament Proteins genetics
Transport Vesicles metabolism
Vesicular Transport Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1551
- Volume :
- 33
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Developmental cell
- Publication Type :
- Academic Journal
- Accession number :
- 25865347
- Full Text :
- https://doi.org/10.1016/j.devcel.2015.02.009