Ventralization of the Drosophila embryo by deletion of extracellular leucine-rich repeats in the Toll protein.
Dorsoventral polarity of the Drosophila embryo is established by a signal transduction pathway in which the maternal transmembrane protein Toll appears to function as the receptor for a ventrally localized extracellular ligand. Certain dominant Toll alleles encode proteins that behave as partially ligand-independent receptors, causing embryos containing these proteins to become ventralized. In extracts of embryos derived from mothers carrying these dominant alleles, we detected a polypeptide of approximately 35 kDa in addition to full-length Toll polypeptides with antibodies to Toll. Our biochemical analyses suggest that the smaller polypeptide is a truncated form of Toll lacking extracellular domain sequences. To assay the biological activity of such a shortened form of Toll, we synthesized RNA encoding a mutant polypeptide lacking the leucine-rich repeats that comprise most of Toll's extracellular domain and injected this RNA into embryos. The truncated Toll protein elicited the most ventral cell fate independently of the wild-type Toll protein and its ligand. These results support the view that Toll is a receptor whose extracellular domain regulates the intrinsic signaling activity of its cytoplasmic domain.
Winans
K A
KA
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Hashimoto
C
C
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002462:Cell Membrane / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins; D005260:Female; D017344:Genes, Insect; D007301:Insect Hormones / Q000737:chemistry / Q000502:physiology*; D007930:Leucine / Q000502:physiology; D008024:Ligands; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000502:physiology*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D051193:Toll-Like Receptors
D029721:Drosophila Proteins; D007301:Insect Hormones; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C068721:Tl protein, Drosophila; D051193:Toll-Like Receptors; D007930:Leucine