Activation of Gαi at the Golgi by GIV/Girdin imposes finiteness in Arf1 signaling

I-Chung Lo; Vijay Gupta; Krishna K Midde; Vanessa Taupin; Inmaculada Lopez-Sanchez; Irina Kufareva; Ruben Abagyan; Paul A Randazzo; Marilyn G Farquhar; Pradipta Ghosh

doi:10.1016/j.devcel.2015.02.009

Activation of Gαi at the Golgi by GIV/Girdin imposes finiteness in Arf1 signaling

Dev Cell. 2015 Apr 20;33(2):189-203. doi: 10.1016/j.devcel.2015.02.009. Epub 2015 Apr 9.

Authors

Affiliations

¹ Departments of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
² Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
³ Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
⁴ Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
⁵ Departments of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: [email protected].
⁶ Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: [email protected].

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

ADP-Ribosylation Factor 1 / metabolism*
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
GTP-Binding Protein alpha Subunits, Gi-Go / metabolism*
GTPase-Activating Proteins / metabolism
Golgi Apparatus / metabolism*
HEK293 Cells
HeLa Cells
Humans
Microfilament Proteins / antagonists & inhibitors
Microfilament Proteins / genetics*
Protein Binding
Protein Structure, Tertiary
Protein Transport / physiology
RNA Interference
RNA, Small Interfering
Signal Transduction
Transport Vesicles / metabolism*
Vesicular Transport Proteins / antagonists & inhibitors
Vesicular Transport Proteins / genetics*

Substances

ARFGAP3 protein, human
CCDC88A protein, human
Coatomer Protein
GTPase-Activating Proteins
Microfilament Proteins
RNA, Small Interfering
Vesicular Transport Proteins
GTP-Binding Protein alpha Subunits, Gi-Go
ADP-Ribosylation Factor 1
ADP-Ribosylation Factors
ARFGAP2 protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding