Localization and activation of the Drosophila protease easter require the ER-resident saposin-like protein seele.
Drosophila embryonic dorsal-ventral polarity is generated by a series of serine protease processing events in the egg perivitelline space. Gastrulation Defective processes Snake, which then cleaves Easter, which then processes Spätzle into the activating ligand for the Toll receptor. seele was identified in a screen for mutations that, when homozygous in ovarian germline clones, lead to the formation of progeny embryos with altered embryonic patterning; maternal loss of seele function leads to the production of moderately dorsalized embryos. By combining constitutively active versions of Gastrulation Defective, Snake, Easter, and Spätzle with loss-of-function alleles of seele, we find that Seele activity is dispensable for Spätzle-mediated activation of Toll but is required for Easter, Snake, and Gastrulation Defective to exert their effects on dorsal-ventral patterning. Moreover, Seele function is required specifically for secretion of Easter from the developing embryo into the perivitelline space and for Easter processing. Seele protein resides in the endoplasmic reticulum of blastoderm embryos, suggesting a role in the trafficking of Easter to the perivitelline space, prerequisite to its processing and function. Easter transport to the perivitelline space represents a previously unappreciated control point in the signal transduction pathway that controls Drosophila embryonic dorsal-ventral polarity.
Section of Molecular Cell and Developmental Biology and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA. d.stein@mail.utexas.edu
David
D
Stein
Iphigenie
I
Charatsi
Yong Suk
YS
Cho
Zhenyu
Z
Zhang
Jesse
J
Nguyen
Robert
R
DeLotto
Stefan
S
Luschnig
Bernard
B
Moussian
D000818:Animals; D019521:Body Patterning / Q000235:genetics; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004789:Enzyme Activation; D049452:Green Fluorescent Proteins / Q000032:analysis; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000032:analysis; D012697:Serine Endopeptidases / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism
D029721:Drosophila Proteins; D011993:Recombinant Fusion Proteins; C068721:Tl protein, Drosophila; D051193:Toll-Like Receptors; C556583:sel protein, Drosophila; C086179:spz protein, Drosophila; D049452:Green Fluorescent Proteins; D012697:Serine Endopeptidases; C078099:ea protein, Drosophila