title: RhoL controls invasion and Rap1 localization during immune cell transmigration in Drosophila.
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.
authors.affiliation: HHMI and Kimmel Center for Biology and Medicine of the Skirball Institute, Department of Cell Biology, New York University School of Medicine, New York, New York 10016-6481, USA.
authors.forename: Daria
authors.initials: D
authors.lastname: Siekhaus
authors.forename: Martin
authors.initials: M
authors.lastname: Haesemeyer
authors.forename: Olivia
authors.initials: O
authors.lastname: Moffitt
authors.forename: Ruth
authors.initials: R
authors.lastname: Lehmann
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002477:Cells / Q000378:metabolism*; D022082:Cellular Structures / Q000378:metabolism; D004330:Drosophila / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D016023:Integrins / Q000378:metabolism* / Q000502:physiology*; D011247:Pregnancy
chemical_list: D015820:Cadherins; D016023:Integrins