Reference Report

Reference
Citation	Huelsmann, S., Hepper, C., Marchese, D., Knoll, C., Reuter, R. (2006). The PDZ-GEF dizzy regulates cell shape of migrating macrophages via Rap1 and integrins in the Drosophila embryo. Development 133(15): 2915--2924. (Export to RIS)
FlyBase ID	FBrf0192108
Publication Type	Research paper
PubMed ID	16818452
PubMed 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.
DOI	10.1242/dev.02449
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Secondary IDs
Language of Publication	English
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Parent Publication
Publication Type	Journal
Abbreviation	Development
Title	Development
Publication Year	1987-
ISBN/ISSN	0950-1991
Data from Reference
Aberrations (1)
	Df(2L)BSC5
Alleles (25)
	Act5C^{Scer\UAS.T:Avic\GFP} Avic\GFP^{S65T.Scer\UAS} BacA\p35^Scer\UAS.cHa Cdc42^N17.Scer\UAS mys¹¹ PDZ-GEF^{dsRNA.Scer\UAS} PDZ-GEF^EP388 PDZ-GEF^k13720 PDZ-GEF^P-RV4 PDZ-GEF^Δ1 PDZ-GEF^Δ3 PDZ-GEF^Δ5 PDZ-GEF^Δ7 PDZ-GEF^Δ8 PDZ-GEF^Δ10 PDZ-GEF^Δ12 R^{N17.Scer\UAS.T:Hsap\MYC} R^P5709 R^{Scer\UAS.T:Hsap\MYC} R^{V12.Scer\UAS.T:Hsap\MYC} Rac1^N17.Scer\UAS Rho1^N19.Scer\UAS Rnor\CD2^{Scer\UAS.cDBa} Scer\GAL4^da.G32 Scer\GAL4^srp
Constructs (13)
	P{GAL4-da.G32} P{srp-Gal4} P{UAS-Act5C.T:GFP} P{UAS-CD2} P{UAS-Cdc42.N17} P{UAS-dizzy.ds} P{UAS-GFP.S65T} P{UAS-p35.H} P{UAS-R.Myc} P{UAS-R.N17} P{UAS-R.V12} P{UAS-Rac1.N17} P{UAS-Rho1.N19}
Genes (11)
	Act5C Avic\GFP BacA\p35 Cdc42 mys PDZ-GEF R Rac1 Rho1 Rnor\CD2 Scer\GAL4
Insertions (2)
	P{EP}PDZ-GEF^EP388 P{lacW}PDZ-GEF^k13720
Natural transposons (1)
	P-element