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Open Access Research article

GxcC connects Rap and Rac signaling during Dictyostelium development

Katarzyna Plak1, Douwe Veltman2, Fabrizia Fusetti3, Jetze Beeksma1, Francisco Rivero4, Peter JM Van Haastert1 and Arjan Kortholt1*

Author Affiliations

1 Department of Cell Biochemistry, University of Groningen, Nijenborgh 7, Groningen, AG, 9747, The Netherlands

2 Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK

3 Department of Biochemistry, Netherlands Proteomics Centre, Groningen Biomolecular Sciences and Biotechnology Institute & Zernike Institute for Advanced Materials, University of Groningen, Groningen, AG, 9747, The Netherlands

4 Centre for Cardiovascular and Metabolic Research, The Hull York Medical School and Department of Biological Sciences, University of Hull, Hull, HU6 7RX, UK

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BMC Cell Biology 2013, 14:6  doi:10.1186/1471-2121-14-6

Published: 30 January 2013

Abstract

Background

Rap proteins belong to the Ras family of small G-proteins. Dictyostelium RapA is essential and implicated in processes throughout the life cycle. In early development and chemotaxis competent cells RapA induces pseudopod formation by activating PI3K and it regulates substrate attachment and myosin disassembly via the serine/threonine kinase Phg2. RapA is also important in late development, however so far little is known about the downstream effectors of RapA that play a role in this process.

Results

Here we show that cells expressing constitutively active RapA exhibit a high level of Rac activation. With a pull-down screen coupled to mass spectrometry, we identified the Rac specific guanine nucleotide exchange factor, GxcC, as Rap binding partner. GxcC binds directly and specifically to active RapA and binds to a subset of Dictyostelium Rac proteins. Deletion studies revealed that this pathway is involved in regulating Dictyostelium development.

Conclusions

GxcC provides a novel link between Rap and Rac signalling and is one of the Rap effectors regulating the progression of multicellular development.

Keywords:
Rap; Rac; GEF; Development; Dictyostelium