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Open Access Research

The cytohesin paralog Sec7 of Dictyostelium discoideum is required for phagocytosis and cell motility

Rolf Müller1, Claudia Herr1, Salil K Sukumaran1, Napoleon Nosa Omosigho1, Markus Plomann2, Tanja Y Riyahi1*, Maria Stumpf1, Karthic Swaminathan1, Marios Tsangarides1, Kyriacos Yiannakou1, Rosemarie Blau-Wasser1, Christoph Gallinger3, Michael Schleicher3, Waldemar Kolanus4 and Angelika A Noegel1*

Author Affiliations

1 Institute of Biochemistry I, Medical Faculty, Center for Molecular Medicine Cologne (CMMC) and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Köln, Germany

2 Institute of Biochemistry II, Medical Faculty, University of Cologne, 50931 Köln, Germany

3 Institute of Anatomy and Cell Biology, Ludwig-Maximilians-University, 80336 München, Germany

4 Laboratory of Molecular Immunology, LIMES Institute of the University of Bonn, Bonn, Germany

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Cell Communication and Signaling 2013, 11:54  doi:10.1186/1478-811X-11-54

Published: 1 August 2013

Abstract

Background

Dictyostelium harbors several paralogous Sec7 genes that encode members of three subfamilies of the Sec7 superfamily of guanine nucleotide exchange factors. One of them is the cytohesin family represented by three members in D. discoideum, SecG, Sec7 and a further protein distinguished by several transmembrane domains. Cytohesins are characterized by a Sec7-PH tandem domain and have roles in cell adhesion and migration.

Results

We study here Sec7. In vitro its PH domain bound preferentially to phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2), phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3). When following the distribution of GFP-Sec7 in vivo we observed the protein in the cytosol and at the plasma membrane. Strikingly, when cells formed pseudopods, macropinosomes or phagosomes, GFP-Sec7 was conspicuously absent from areas of the plasma membrane which were involved in these processes. Mutant cells lacking Sec7 exhibited an impaired phagocytosis and showed significantly reduced speed and less persistence during migration. Cellular properties associated with mammalian cytohesins like cell-cell and cell-substratum adhesion were not altered. Proteins with roles in membrane trafficking and signal transduction have been identified as putative interaction partners consistent with the data obtained from mutant analysis.

Conclusions

Sec7 is a cytosolic component and is associated with the plasma membrane in a pattern distinctly different from the accumulation of PI(3,4,5)P3. Mutant analysis reveals that loss of the protein affects cellular processes that involve membrane flow and the actin cytoskeleton.

Keywords:
ARFGEF; Cell adhesion; Cell migration; Phagocytosis; Phosphoinositide binding