Reference Report

Reference
Citation	Siekhaus, D., Haesemeyer, M., Moffitt, O., Lehmann, R. (2010). RhoL controls invasion and Rap1 localization during immune cell transmigration in Drosophila. Nat. Cell Biol. 12(6): 605--610. (Export to RIS)
FlyBase ID	FBrf0210888
Publication Type	Research paper
PubMed ID	20495554
PubMed Abstract	Human immune cells have to penetrate an endothelial barrier during their beneficial pursuit of infection and their destructive infiltration of tissues in autoimmune diseases. This transmigration requires Rap1 GTPase to activate integrin affinity. We define a new model system for this process by demonstrating, with live imaging and genetics, that during embryonic development Drosophila melanogaster immune cells penetrate an epithelial, Drosophila E-cadherin (DE-cadherin)-based tissue barrier. A mutant in RhoL, a GTPase homologue that is specifically expressed in haemocytes, blocks this invasive step but not other aspects of guided migration. RhoL mediates integrin adhesion caused by Drosophila Rap1 overexpression and moves Rap1 away from a concentration in the cytoplasm to the leading edge during invasive migration. These findings indicate that a programmed migratory step during Drosophila development bears striking molecular similarities to vertebrate immune cell transmigration during inflammation, and identify RhoL as a new regulator of invasion, adhesion and Rap1 localization. Our work establishes the utility of Drosophila for identifying novel components of immune cell transmigration and for understanding the in vivo interplay of immune cells with the barriers they penetrate.
DOI	10.1038/ncb2063
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Nat. Cell Biol.
Title	Nature Cell Biology
Publication Year	1999-
ISBN/ISSN	1465-7392 1476-4679
Data from Reference
Aberrations (2)
	Df(2L)BSC185 Df(3R)by416
Alleles (20)
	Avic\GFP^{E.Scer\UAS.T:Uuuu\Myr4} Avic\GFP^Scer\UAS.cUa BacA\p35^Scer\UAS.cHa Ecol\lacZ^{Scer\UAS.T:SV40\nls2} if^B2 Mmp1^Q112stop Mmp2^W307stop PDZ-GEF^Δ1 Pvr¹ R^T:Avic\GFP R^{V12.cHa.Scer\UAS} Reck^Scer\UAS.cSa RhoL^10-161 RhoL^Scer\UAS.cSa RhoL^XA12 Scer\GAL4^8-169 Scer\GAL4^srp.Hemo shg^k03401 shg^{Ubi-p63E.T:Avic\GFP-rs} Timp^Scer\UAS.cSa
Constructs (12)
	P{GawB} P{R^T:Avic\GFP} P{srp.Hemo-GAL4} P{UAS-GFP.U} P{UAS-lacZ.NZ} P{UAS-p35.H} P{UAS-Rap1.V12.H} P{UAS-Reck.S} P{UAS-RhoL.S} P{UAS-srcEGFP} P{UAS-Timp.S} P{Ubi-p63E-shg.GFP}
Genes (20)
	Avic\GFP BacA\p35 Cdc42 Ecol\lacZ if Mmp1 Mmp2 Moe PDZ-GEF Pvf2 Pvf3 Pvr R Rac1 Reck RhoL Scer\GAL4 shg srp Timp
Insertions (2)
	P{GawB}8-163 P{GawB}RhoL^10-161
Natural transposons (1)
	P-element