The Pdz-gef Dizzy Regulates Cell Shape of Migrating Macrophages Via Rap1 and Integrins in the Drosophila Embryo.
From: Interfakultäres Institut für Zellbiologie, Abteilung Genetik der Tiere, Fakultät für Biologie, Universität Tübingen, Auf der Morgenstelle 28, D-72076 Tübingen, Germany.
Development (Cambridge, England)
- Publish Date: Aug 2006
- ISSN: 0950-1991
- Volume: 133
- Issue: 15
- Pages: 2915-24
- Medium: Print
- Language: English
- Citation (JAMA): Huelsmann Sven, Hepper Christina, Marchese Daniele, et al. The Pdz-gef Dizzy Regulates Cell Shape of Migrating Macrophages Via Rap1 and Integrins in the Drosophila Embryo.. Development Aug 2006;133:2915-24
Abstract
In Drosophila embryos, macrophages originate from the cephalic mesoderm and perform a complex migration throughout the entire embryo. The molecular mechanisms regulating this cell migration remain largely unknown. We identified the Drosophila PDZ G-nucleotide exchange factor (PDZ-GEF) Dizzy as a component essential for normal macrophage migration. In mutants lacking Dizzy, macrophages have smaller cellular protrusions, and their migration is slowed down significantly. This phenotype appears to be cell-autonomous, as it is also observed in embryos with a dsRNA-induced reduction of dizzy function in macrophages. In a complementary fashion, macrophages overexpressing Dizzy are vastly extended and form very long protrusions. These cell shape changes depend on the function of the small GTPase Rap1: in rap1 mutants, Dizzy is unable to induce the large protrusions. Furthermore, forced expression of a dominant-active form of Rap1, but not of the wild-type form, induces similar cell shape changes as Dizzy does overexpression. These findings suggest that Dizzy acts through Rap1. We propose that integrin-dependent adhesion is a Rap1-mediated target of Dizzy activity: in integrin mutants, neither Dizzy nor Rap1 can induce cell shape changes in macrophages. These data provide the first link between a PDZ-GEF, the corresponding small GTPase and integrin-dependent cell adhesion during cell migration in embryonic development.
Mesh Headings (Keywords): Animals, Animals, Genetically Modified, Cell Adhesion, Cell Movement, Cell Shape, DNA, DNA Primers, Drosophila, Drosophila Proteins, Embryo, Nonmammalian, Genome, Guanine Nucleotide Exchange Factors, Integrins, Macrophages, rap1 GTP-Binding Proteins
Check for Full Text / PubMed Unique Identifier (PMID): 16818452
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