title: A ventrally localized protease in the Drosophila egg controls embryo dorsoventral polarity.
abstract: Drosophila embryo dorsoventral (DV) polarity is defined by serine protease activity in the perivitelline space (PVS) between the embryonic membrane and the inner layer of the eggshell. Gastrulation Defective (GD) cleaves and activates Snake (Snk). Activated Snk cleaves and activates Easter (Ea), exclusively on the ventral side of the embryo. Activated Ea then processes Spätzle (Spz) into the activating ligand for Toll, a transmembrane receptor that is distributed throughout the embryonic plasma membrane. Ventral activation of Toll depends upon the activity of the Pipe sulfotransferase in the ventral region of the follicular epithelium that surrounds the developing oocyte. Pipe transfers sulfate residues to several protein components of the inner vitelline membrane layer of the eggshell. Here we show that GD protein becomes localized in the ventral PVS in a Pipe-dependent process. Moreover, ventrally concentrated GD acts to promote the cleavage of Ea by Snk through an extracatalytic mechanism that is distinct from GD's proteolytic activation of Snk. Together, these observations illuminate the mechanism through which spatially restricted sulfotransferase activity in the developing egg chamber leads to localization of serine protease activity and ultimately to spatially specific activation of the Toll receptor in the Drosophila embryo.
authors.affiliation: Section of Molecular Cell and Developmental Biology and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX, 78712, USA.
authors.forename: Yong Suk
authors.initials: YS
authors.lastname: Cho
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Stevens
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Sieverman
authors.forename: Jesse
authors.initials: J
authors.lastname: Nguyen
authors.forename: David
authors.initials: D
authors.lastname: Stein
mesh_terms: D000818:Animals; D019521:Body Patterning; D004330:Drosophila / Q000196:embryology* / Q000201:enzymology; D029721:Drosophila Proteins / Q000378:metabolism*; D047108:Embryonic Development; D005260:Female; D010063:Ovum / Q000201:enzymology; D012697:Serine Endopeptidases / Q000378:metabolism*; D015238:Sulfotransferases / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C068721:Tl protein, Drosophila; D051193:Toll-Like Receptors; D015238:Sulfotransferases; D012697:Serine Endopeptidases; C078099:ea protein, Drosophila; C440488:gd protein, Drosophila; C081508:snk protein, Drosophila