A Drosophila homologue of membrane-skeleton protein 4.1 is associated with septate junctions and is encoded by the coracle gene.

Protein 4.1 functions to link transmembrane proteins with the underlying spectrin/actin cytoskeleton. To permit a genetic analysis of the developmental role and cellular functions of this membrane-skeletal protein, we have identified and characterized its Drosophila homologue (termed D4.1). D4.1 is localized to the septate junctions of epithelial cells and is encoded by the coracle gene, a new locus whose primary mutant phenotype is a failure in dorsal closure. In addition, coracle mutations dominantly suppress Ellipse, a hypermorphic allele of the Drosophila EGF-receptor homologue. These data indicate that D4.1 is associated with the septate junction, and suggest that it may play a role in cell-cell interactions that are essential for normal development.

[1]  K. Sakaguchi,et al.  The ezrin-like family of tyrosine kinase substrates: receptor-specific pattern of tyrosine phosphorylation and relationship to malignant transformation. , 1993, Oncogene.

[2]  C. V. Van Itallie,et al.  The tight junction protein ZO-1 is homologous to the Drosophila discs-large tumor suppressor protein of septate junctions. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[3]  T. Leto,et al.  Mechanisms of cytoskeletal regulation: Modulation of aortic endothelial cell protein band 4.1 by the extracellular matrix , 1986, Journal of cellular physiology.

[4]  V. Marchesi,et al.  Regulation of the association of membrane skeletal protein 4.1 with glycophorin by a polyphosphoinositide , 1985, Nature.

[5]  Sarah E. Ades,et al.  Sequence and domain structure of talin , 1990, Nature.

[6]  I. Correas Characterization of isoforms of protein 4.1 present in the nucleus. , 1991, The Biochemical journal.

[7]  P. Bertics,et al.  Phosphorylation of protein 4.1 on tyrosine-418 modulates its function in vitro. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[8]  R. J. Fleming,et al.  Specific EGF repeats of Notch mediate interactions with Delta and serrate: Implications for notch as a multifunctional receptor , 1991, Cell.

[9]  P. Simpson Growth and cell competition in Drosophila , 1981 .

[10]  K. Kinzler,et al.  A gene for neurofibromatosis 2 , 1993, Nature.

[11]  J. Conboy,et al.  Tissue- and development-specific alternative RNA splicing regulates expression of multiple isoforms of erythroid membrane protein 4.1. , 1991, The Journal of biological chemistry.

[12]  J. Conboy,et al.  Multiple protein 4.1 isoforms produced by alternative splicing in human erythroid cells. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[13]  B. Shilo,et al.  Localization of DER and the pattern of cell divisions in wild-type and Ellipse eye imaginal discs. , 1992, Developmental biology.

[14]  M. Arpin,et al.  Ezrin contains cytoskeleton and membrane binding domains accounting for its proposed role as a membrane-cytoskeletal linker , 1993, The Journal of cell biology.

[15]  C. Goodman,et al.  Cell and substrate adhesion molecules in Drosophila. , 1991, Annual review of cell biology.

[16]  B. Shilo,et al.  The Drosophila EGF receptor homolog (DER) gene is allelic to faint little ball, a locus essential for embryonic development , 1989, Cell.

[17]  L. Goldstein,et al.  Characterization and use of the Drosophila metallothionein promoter in cultured Drosophila melanogaster cells. , 1988, Nucleic acids research.

[18]  V. Marchesi,et al.  Stabilizing infrastructure of cell membranes. , 1985, Annual review of cell biology.

[19]  J. Conboy,et al.  Hereditary elliptocytosis due to both qualitative and quantitative defects in membrane skeletal protein 4.1. , 1991, Blood.

[20]  C. Nüsslein-Volhard,et al.  The origin of pattern and polarity in the Drosophila embryo , 1992, Cell.

[21]  V. Marchesi,et al.  Heterogeneity of mRNA and protein products arising from the protein 4.1 gene in erythroid and nonerythroid tissues , 1990, The Journal of cell biology.

[22]  P. Bryant,et al.  Apical junctions and cell signalling in epithelia , 1993, Journal of Cell Science.

[23]  G. Meer,et al.  The function of tight junctions in maintaining differences in lipid composition between the apical and the basolateral cell surface domains of MDCK cells. , 1986, The EMBO journal.

[24]  Y. Takakuwa,et al.  Localization of proteins immunologically related to erythrocyte protein 4.1, spectrin and ankyrin in thyroid gland. , 1992, Acta Histochemica.

[25]  Tian Xu,et al.  Molecular interactions between the protein products of the neurogenic loci Notch and Delta, two EGF-homologous genes in Drosophila , 1990, Cell.

[26]  V. Hartenstein,et al.  The development of cellular junctions in the Drosophila embryo. , 1994, Developmental biology.

[27]  D. Kiehart,et al.  Morphogenesis in Drosophila requires nonmuscle myosin heavy chain function. , 1993, Genes & development.

[28]  S. Artavanis-Tsakonas,et al.  Specific truncations of Drosophila Notch define dominant activated and dominant negative forms of the receptor , 1993, Cell.

[29]  N. Kley,et al.  A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. , 1993, Cell.

[30]  M. Peifer,et al.  The segment polarity gene armadillo encodes a functionally modular protein that is the Drosophila homolog of human plakoglobin , 1990, Cell.

[31]  Peter J. Bryant,et al.  The discs-large tumor suppressor gene of Drosophila encodes a guanylate kinase homolog localized at septate junctions , 1991, Cell.

[32]  V. Marchesi,et al.  Selective expression of an erythroid-specific isoform of protein 4.1. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[33]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[34]  M. Ashburner Drosophila. A laboratory manual. , 1989 .

[35]  M. Peifer,et al.  The product of the Drosophila segment polarity gene armadillo is part of a multi-protein complex resembling the vertebrate adherens junction. , 1993, Journal of cell science.

[36]  J. Conboy,et al.  An isoform-specific mutation in the protein 4.1 gene results in hereditary elliptocytosis and complete deficiency of protein 4.1 in erythrocytes but not in nonerythroid cells. , 1993, The Journal of clinical investigation.

[37]  C. Noirot,et al.  Septate and scalariform junctions in arthropods. , 1980, International review of cytology.

[38]  R. J. Fleming,et al.  The Notch locus and the genetic circuitry involved in early Drosophila neurogenesis. , 1990, Genes & development.

[39]  G. Rubin,et al.  Ras1 and a putative guanine nucleotide exchange factor perform crucial steps in signaling by the sevenless protein tyrosine kinase , 1991, Cell.

[40]  G. Rubin,et al.  Localization of the sevenless protein, a putative receptor for positional information, in the eye imaginal disc of Drosophila , 1987, Cell.

[41]  J. Siliciano,et al.  Identification of ZO-1: a high molecular weight polypeptide associated with the tight junction (zonula occludens) in a variety of epithelia , 1986, The Journal of cell biology.

[42]  V. Bennett,et al.  The spectrin-actin junction of erythrocyte membrane skeletons. , 1989, Biochimica et biophysica acta.

[43]  S. Zipursky,et al.  Induction in the developing compound eye of Drosophila: Multiple mechanisms restrict R7 induction to a single retinal precursor cell , 1991, Cell.

[44]  Richard A. Anderson,et al.  Glycophorin is linked by band 4.1 protein to the human erythrocyte membrane skeleton , 1984, Nature.

[45]  S. Artavanis-Tsakonas,et al.  Complex cellular and subcellular regulation of notch expression during embryonic and imaginal development of Drosophila: implications for notch function , 1991, The Journal of cell biology.

[46]  J. Lis,et al.  Structure and expression of ubiquitin genes of Drosophila melanogaster , 1988, Molecular and cellular biology.

[47]  L. Kauvar,et al.  The engrailed locus of drosophila: Structural analysis of an embryonic transcript , 1985, Cell.

[48]  S. Pulst,et al.  Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2 , 1993, Nature.

[49]  G. Pasternack,et al.  Erythrocyte protein 4.1 binds and regulates myosin. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[50]  D. Smith,et al.  Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. , 1988, Gene.