Golgi-Resident Gαo Promotes Protrusive Membrane Dynamics

Gonzalo P Solis; Oleksii Bilousov; Alexey Koval; Anne-Marie Lüchtenborg; Chen Lin; Vladimir L Katanaev

doi:10.1016/j.cell.2017.07.015

Golgi-Resident Gαo Promotes Protrusive Membrane Dynamics

Cell. 2017 Aug 24;170(5):939-955.e24. doi: 10.1016/j.cell.2017.07.015. Epub 2017 Aug 10.

Authors

Gonzalo P Solis¹, Oleksii Bilousov², Alexey Koval², Anne-Marie Lüchtenborg², Chen Lin², Vladimir L Katanaev³

Affiliations

¹ Department of Pharmacology and Toxicology, University of Lausanne, CH-1011 Lausanne, Switzerland. Electronic address: gonzalo.solis@unil.ch.
² Department of Pharmacology and Toxicology, University of Lausanne, CH-1011 Lausanne, Switzerland.
³ Department of Pharmacology and Toxicology, University of Lausanne, CH-1011 Lausanne, Switzerland; School of Biomedicine, Far Eastern Federal University, Vladivostok 690950, Russian Federation. Electronic address: vladimir.katanaev@unil.ch.

PMID: 28803726
DOI: 10.1016/j.cell.2017.07.015

Abstract

To form protrusions like neurites, cells must coordinate their induction and growth. The first requires cytoskeletal rearrangements at the plasma membrane (PM), the second requires directed material delivery from cell's insides. We find that the Gαo-subunit of heterotrimeric G proteins localizes dually to PM and Golgi across phyla and cell types. The PM pool of Gαo induces, and the Golgi pool feeds, the growing protrusions by stimulated trafficking. Golgi-residing KDELR binds and activates monomeric Gαo, atypically for G protein-coupled receptors that normally act on heterotrimeric G proteins. Through multidimensional screenings identifying > 250 Gαo interactors, we pinpoint several basic cellular activities, including vesicular trafficking, as being regulated by Gαo. We further find small Golgi-residing GTPases Rab1 and Rab3 as direct effectors of Gαo. This KDELR → Gαo → Rab1/3 signaling axis is conserved from insects to mammals and controls material delivery from Golgi to PM in various cells and tissues.

Keywords: Drosophila melanogaster; G protein coupled receptors; Golgi apparatus; Gαo interactome; KDEL receptor; Rab1/3 GTPases; heterotrimeric G proteins; neurite outgrowth; protrusion formation; vesicular trafficking.

MeSH terms

Animals
Cell Line
Cell Membrane / metabolism*
Cell Surface Extensions / metabolism*
Drosophila
Female
GTP Phosphohydrolases / metabolism
GTP-Binding Protein alpha Subunits, Gi-Go / metabolism*
Golgi Apparatus / metabolism*
Humans
Male
Mice
Mice, Inbred C57BL
Neurites / metabolism
Receptors, G-Protein-Coupled / metabolism
Receptors, Peptide / metabolism
Two-Hybrid System Techniques
rab1 GTP-Binding Proteins / metabolism
rab3 GTP-Binding Proteins / metabolism

Substances

Receptors, G-Protein-Coupled
Receptors, Peptide
GTP Phosphohydrolases
GTP-Binding Protein alpha Subunits, Gi-Go
rab1 GTP-Binding Proteins
rab3 GTP-Binding Proteins