Cleavage and secretion is not required for Four-jointed function in Drosophila patterning

four-jointed (fj) is required for proximodistal growth and planar polarity in Drosophila tissues. It encodes a predicted type II transmembrane protein with putative signal peptidase sites in its transmembrane domain, and its C terminus is secreted. Fj has therefore been proposed to act as a secreted signalling molecule. We show that Fj protein has a graded distribution in eye and wing imaginal discs, and is largely localised to the Golgi in vivo and in transfected cells. Forms of Fj that are constitutively secreted or anchored in the Golgi were assayed for function in vivo. We find that cleavage and secretion of Fj is not necessary for activity, and that Golgi-anchored Fj has increased activity over wild type. fj has similar phenotypes to those caused by mutations in the cadherin-encoding genes fat (ft) and dachsous (ds). We show that fj interacts genetically with ft and ds in planar polarity and proximodistal patterning. We propose that Fj may act in the Golgi to regulate the activity of Ft and Ds.

[1]  J. Charlton,et al.  Mutations in the cadherin superfamily member gene dachsous cause a tissue polarity phenotype by altering frizzled signaling. , 1998, Development.

[2]  J. Villano,et al.  four-jointed is required for intermediate growth in the proximal-distal axis in Drosophila. , 1995, Development.

[3]  D. Paterson,et al.  Similarities in sequences and cellular expression between rat CD2 and CD4 antigens , 1987, The Journal of experimental medicine.

[4]  C. Goodman,et al.  Dachsous encodes a member of the cadherin superfamily that controls imaginal disc morphogenesis in Drosophila. , 1995, Genes & development.

[5]  Jeffrey D. Axelrod,et al.  Fidelity in planar cell polarity signalling , 2003, Nature.

[6]  P. Ingham,et al.  Transcriptional activation of hedgehog target genes in Drosophila is mediated directly by the cubitus interruptus protein, a member of the GLI family of zinc finger DNA-binding proteins. , 1996, Genes & development.

[7]  T. Tabata,et al.  Hedgehog is a signaling protein with a key role in patterning Drosophila imaginal discs , 1994, Cell.

[8]  H. Steller,et al.  Positional information along the dorsal-ventral axis of the Drosophila eye: graded expression of the four-jointed gene. , 1996, Developmental biology.

[9]  R. Doolittle,et al.  A simple method for displaying the hydropathic character of a protein. , 1982, Journal of molecular biology.

[10]  N. Perrimon,et al.  Multiple roles for four-jointed in planar polarity and limb patterning. , 2000, Developmental biology.

[11]  P. O’Farrell,et al.  A cell-autonomous, ubiquitous marker for the analysis of Drosophila genetic mosaics. , 1994, Developmental Biology.

[12]  P. Beachy,et al.  Secretion and localized transcription suggest a role in positional signaling for products of the segmentation gene hedgehog , 1992, Cell.

[13]  J. Gerhart,et al.  The effect of growth and joint formation on bristle pattern in D. melanogaster. , 1976, The Journal of experimental zoology.

[14]  T. Wolff,et al.  The Cadherins Fat and Dachsous Regulate Dorsal/Ventral Signaling in the Drosophila Eye , 2002, Current Biology.

[15]  P. Lawrence,et al.  Developmental Compartments and Planar Polarity in Drosophila , 2002, Current Biology.

[16]  N. Perrimon,et al.  The four-jointed gene is required in the Drosophila eye for ommatidial polarity specification , 1999, Current Biology.

[17]  A. Mccarthy.  Development , 1996, Current Opinion in Neurobiology.

[18]  S. Cohen,et al.  Glycosyltransferase activity of Fringe modulates Notch–Delta interactions , 2000, Nature.

[19]  Erik L. L. Sonnhammer,et al.  A Hidden Markov Model for Predicting Transmembrane Helices in Protein Sequences , 1998, ISMB.

[20]  J. Villano,et al.  Four-jointed interacts with dachs, abelson and enabled and feeds back onto the Notch pathway to affect growth and segmentation in the Drosophila leg. , 2001, Development.

[21]  David Strutt,et al.  Nonautonomous planar polarity patterning in Drosophila: dishevelled-independent functions of frizzled. , 2002, Developmental cell.

[22]  V. Malhotra,et al.  The mechanism of Golgi segregation during mitosis is cell type-specific. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[23]  Jeffrey D. Axelrod,et al.  Regulation of Frizzled by Fat-like Cadherins during Planar Polarity Signaling in the Drosophila Compound Eye , 2002, Cell.

[24]  G. Rubin,et al.  Analysis of genetic mosaics in developing and adult Drosophila tissues. , 1993, Development.

[25]  M. Bate,et al.  The development of Drosophila melanogaster , 1993 .

[26]  S. Cohen,et al.  Two distinct mechanisms for long-range patterning by Decapentaplegic in the Drosophila wing , 1996, Nature.

[27]  S. Munro,et al.  The Notch signalling regulator Fringe acts in the Golgi apparatus and requires the glycosyltransferase signature motif DxD , 2000, Current Biology.

[28]  D. Yamamoto,et al.  The Drosophila mushroom body is a quadruple structure of clonal units each of which contains a virtually identical set of neurones and glial cells. , 1997, Development.

[29]  E. Bennett,et al.  cDNA cloning and expression of a novel human UDP-N-acetyl-alpha-D-galactosamine. Polypeptide N-acetylgalactosaminyltransferase, GalNAc-t3. , 1996, The Journal of biological chemistry.

[30]  G. Heijne.  A new method for predicting signal sequence cleavage sites. , 1986 .

[31]  Peter J. Bryant,et al.  The fat tumor suppressor gene in Drosophila encodes a novel member of the cadherin gene superfamily , 1991, Cell.

[32]  G. von Heijne,et al.  A new method for predkting signal sequence cleavage sites , 2022 .

[33]  Manuel Calleja,et al.  Two distinct mechanisms for long-range patterning by Decapentaplegic in the Drosophila wing , 1996, Nature.

[34]  S. Brunak,et al.  SHORT COMMUNICATION Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites , 1997 .

[35]  N. Perrimon,et al.  Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. , 1993, Development.

[36]  M. Gessler,et al.  Fjx1, the murine homologue of the Drosophila four-jointed gene, codes for a putative secreted protein expressed in restricted domains of the developing and adult brain , 1999, Mechanisms of Development.