A direct and functional interaction between Go and Rab5 during G protein-coupled receptor signaling.

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Version: Final published version
Serval ID
serval:BIB_9E5634A3124D
Type
Article: article from journal or magazin.
Collection
Publications
Title
A direct and functional interaction between Go and Rab5 during G protein-coupled receptor signaling.
Journal
Science Signaling
Author(s)
Purvanov V., Koval A., Katanaev V.L.
ISSN
1937-9145 (Electronic)
Publication state
Published
Issued date
2010
Volume
3
Number
136
Pages
ra65
Language
english
Abstract
Rab5 is a small guanosine triphosphatase (GTPase) that regulates the early stages of endocytosis and is conserved in eukaryotes. Rab5 regulates the internalization of receptors and other membrane-associated signaling proteins. The function of Rab5 in these processes is considered relatively passive, so that the endocytic capacity of Rab5 is used during, for example, beta-arrestin-dependent internalization of G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors (GPCRs). Direct recruitment or activation of Rab5 by the components of these signaling pathways has not been reported. Here, we demonstrate an interaction of Drosophila Rab5 and an immediate transducer of GPCR signaling, the G protein G(o), in vitro and in vivo. Rab5 and G(o) bound to each other as purified proteins, as well as in fly extracts. In cellular assays, G(o) led to Rab5 activation and endosome fusion. We further showed that the G(o)-Rab5 interaction functioned in Drosophila planar cell polarity and Wingless signal transduction, pathways initiated by GPCRs of the Frizzled (Fz) family. Additionally, the recycling Rab GTPases Rab4 and Rab11 functioned in Fz- and G(o)-mediated signaling to favor planar cell polarity over canonical Wingless signaling. The interplay between heterotrimeric G proteins and Rab GTPases controlled receptor internalization, revealing a previously uncharacterized regulatory mechanism in GPCR signaling.
Keywords
Animals, Cell Polarity/physiology, Drosophila Proteins/genetics, Drosophila Proteins/metabolism, Drosophila melanogaster, Endocytosis/physiology, Endosomes/genetics, Endosomes/metabolism, GTP-Binding Protein alpha Subunits, Gi-Go/genetics, GTP-Binding Protein alpha Subunits, Gi-Go/metabolism, Protein Binding, Receptors, G-Protein-Coupled/genetics, Receptors, G-Protein-Coupled/metabolism, Signal Transduction/physiology, Wnt1 Protein/genetics, Wnt1 Protein/metabolism, rab GTP-Binding Proteins/genetics, rab GTP-Binding Proteins/metabolism, rab4 GTP-Binding Proteins/genetics, rab4 GTP-Binding Proteins/metabolism, rab5 GTP-Binding Proteins/genetics, rab5 GTP-Binding Proteins/metabolism
Pubmed
Web of science
Create date
22/12/2011 16:12
Last modification date
20/08/2019 15:04
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