Drosophila lowfat, a novel modulator of Fat signaling.
The Fat-Hippo-Warts signaling network regulates both transcription and planar cell polarity. Despite its crucial importance to the normal control of growth and planar polarity, we have only a limited understanding of the mechanisms that regulate Fat. We report here the identification of a conserved cytoplasmic protein, Lowfat (Lft), as a modulator of Fat signaling. Drosophila Lft, and its human homologs LIX1 and LIX1-like, bind to the cytoplasmic domains of the Fat ligand Dachsous, the receptor protein Fat, and its human homolog FAT4. Lft protein can localize to the sub-apical membrane in disc cells, and this membrane localization is influenced by Fat and Dachsous. Lft expression is normally upregulated along the dorsoventral boundary of the developing wing, and is responsible for elevated levels of Fat protein there. Levels of Fat and Dachsous protein are reduced in lft mutant cells, and can be increased by overexpression of Lft. lft mutant animals exhibit a wing phenotype similar to that of animals with weak alleles of fat, and lft interacts genetically with both fat and dachsous. These studies identify Lft as a novel component of the Fat signaling pathway, and the Lft-mediated elevation of Fat levels as a mechanism for modulating Fat signaling.
Mao
Yaopan
Y
Howard Hughes Medical Institute, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers The State University of New Jersey, Piscataway, NJ 08854, USA.
Kucuk
Binnaz
B
Irvine
Kenneth D
KD
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D000071183:Autophagy-Related Proteins; D001483:Base Sequence; D001665:Binding Sites; D015820:Cadherins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D004330:Drosophila / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013045:Species Specificity; D014921:Wings, Animal / Q000254:growth & development / Q000378:metabolism
D000071183:Autophagy-Related Proteins; D015820:Cadherins; D015815:Cell Adhesion Molecules; D017931:DNA Primers; D029721:Drosophila Proteins; C544157:Lft protein, Drosophila; C530882:Lix1 protein, human; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; C094449:ds protein, Drosophila; C472307:ft protein, Drosophila