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Sci. Signal., 24 August 2010
Vol. 3, Issue 136, p. ra65
[DOI: 10.1126/scisignal.2000877]


A Direct and Functional Interaction Between Go and Rab5 During G Protein–Coupled Receptor Signaling

Vladimir Purvanov1, Alexey Koval1, and Vladimir L. Katanaev1,2*

1 Department of Biology, University of Konstanz, Universitätsstrasse 10, Box 643, Konstanz 78457, Germany.
2 Institute of Protein Research, Russian Academy of Sciences, 4 Institutskaya Street, Pushchino 142290, Moscow Region, Russia.

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, β-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 Go, in vitro and in vivo. Rab5 and Go bound to each other as purified proteins, as well as in fly extracts. In cellular assays, Go led to Rab5 activation and endosome fusion. We further showed that the Go-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 Go-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.

* To whom correspondence should be addressed. E-mail: vladimir.katanaev{at}

Citation: V. Purvanov, A. Koval, V. L. Katanaev, A Direct and Functional Interaction Between Go and Rab5 During G Protein–Coupled Receptor Signaling. Sci. Signal. 3, ra65 (2010).

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