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JOURNAL ARTICLES
PAR-6 is a conserved PDZ domain-containing protein that colocalizes with PAR-3 in Caenorhabditis elegans embryos
T.J. Hung, K.J. Kemphues
Development 1999 126: 127-135;

Summary

The par genes are required to establish polarity in the Caenorhabditis elegans embryo. Mutations in two of these genes, par-3 and par-6, exhibit similar phenotypes. A third gene, pkc-3, gives a similar phenotype when the protein is depleted by RNA interference. PAR-3 and PKC-3 protein are colocalized to the anterior periphery of asymmetrically dividing cells of the germline lineage and the peripheral localizations of both proteins depends upon the activity of par-6. Here we report the molecular cloning of par-6 and the immunolocalization of PAR-6 protein. We found that par-6 encodes a PDZ-domain-containing protein and has homologues in mammals and flies. Moreover, we discovered that PAR-6 colocalizes with PAR-3 and that par-3 and pkc-3 activity are required for the peripheral localization of PAR-6. The localization of both PAR-3 and PAR-6 proteins is affected identically by mutations in the par-2, par-4 and par-5 genes. The co-dependence of PAR-3, PAR-6 and PKC-3 for peripheral localization and the overlap in their distributions lead us to propose that they act in a protein complex.

Reference

    1. Bowerman B.,
    2. Draper B. W.,
    3. Mello C. C.,
    4. Priess J. R.
    (1993) The maternal gene skn-1 encodes a protein that is distributed unequally in early C. elegans embryos. Cell 74, 443–452
    OpenUrlCrossRefPubMedWeb of Science
    1. Bowerman B.,
    2. Ingram M. K.,
    3. Hunter C. P.
    (1997) The maternal par genes and the segregation of cell fate specification activities in early Caenorhabditis elegans embryos. Development 124, 3815–3826
    OpenUrlAbstract
    1. Boyd L.,
    2. Guo S.,
    3. Levitan D.,
    4. Stinchcomb D. T.,
    5. Kemphues K. J.
    (1996) PAR-2 is asymmetrically distributed and promotes association of Pgranules and PAR-1 with the cortex in C. elegans embryos. Development 122, 3075–3084
    OpenUrlAbstract
    1. Brenner S.
    (1974) The genetics of Caenorhabditis elegans. Genetics 77, 71–94
    OpenUrlAbstract/FREE Full Text
    1. Crittenden S. L.,
    2. Troemel E. R.,
    3. Evans T. C.,
    4. Kimble J.
    (1994) GLP-1 is localized to the mitotic region of the C. elegans germ line. Development 120, 2901–2911
    OpenUrlAbstract
    1. Doyle D. A.,
    2. Lee A.,
    3. Lewis J.,
    4. Kim E.,
    5. Sheng M.,
    6. MacKinnon R.
    (1996) Crystal structures of a complexed and peptide-free membrane protein-binding domain: Molecular basis of peptide recognition by PDZ. Cell 85, 1067–1076
    OpenUrlCrossRefPubMedWeb of Science
    1. Draper B. W.,
    2. Mello C. C.,
    3. Bowerman B.,
    4. Hardin J.,
    5. Priess J. R.
    (1996) MEX-3 is a KH domain protein that regulates blastomer identity in early C. elegans embryos. Cell 87, 205–216
    OpenUrlCrossRefPubMedWeb of Science
    1. Etemad-Moghadam B.,
    2. Guo S.,
    3. Kemphues K. J.
    (1995) Asymmetrically distributed PAR-3 protein contributes to cell polarity and spindle alignment in early C. elegans embryos. Cell 83, 743–752
    OpenUrlCrossRefPubMedWeb of Science
    1. Evans T. C.,
    2. Crittenden S. L.,
    3. Kodoyianni V.,
    4. Kimble J.
    (1994) Translational control of maternal glp-1 mRNA establishes an asymmetry in the C. elegans embryo. Cell 77, 183–194
    OpenUrlCrossRefPubMedWeb of Science
    1. Guedes S.,
    2. Priess J. R.
    (1997) The C. elegans MEX-1 protein is present in germline blastomeres and is a P granule component. Development 124, 731–739
    OpenUrlAbstract
    1. Guo S.,
    2. Kemphues K. J.
    (1995) par-1, a gene required for establishing polarity in C. elegans embryos encodes a putative ser/thr kinase that is asymmetrically distributed. Cell 81, 611–620
    OpenUrlCrossRefPubMedWeb of Science
    1. Guo S.,
    2. Kemphues K. J.
    (1996) Molecular genetics of asymmetric cleavage in the early Caenorhabditis elegans embryo. Curr. Opin. Gen. Dev 6, 408–415
    OpenUrlCrossRefPubMedWeb of Science
    1. Higgins D. G.,
    2. Sharp P. M.
    (1989) Fast and sensitive multiple sequence alignments on a microcomputer. Comput. Appl. Biosci 5, 151–153
    OpenUrlAbstract/FREE Full Text
    1. Izumi Y.,
    2. Hirose T.,
    3. Tamai Y.,
    4. Hirai S.,
    5. Nagashima Y.,
    6. Fujimoto T.,
    7. Tabuse Y.,
    8. Kemphues K.,
    9. Ohno S.
    (1998) An atypical PKC directly associates and co-localizes at the epithelial tight junction with ASIP, a mammalian homologue of C. elegans polarity protein PAR-3. J. Cell Biol 143, 85–106
    OpenUrl
    1. Kemphues K. J.,
    2. Priess J. R.,
    3. Morton D. G.,
    4. Cheng N.
    (1988) Identification of genes required for cytoplasmic localization in early C. elegans embryos. Cell 52, 311–320
    OpenUrlCrossRefPubMedWeb of Science
    1. Lee J.,
    2. Jongeward G. D.,
    3. Sternberg P. W.
    (1994) unc-101, a gene required from many aspects of Caenorhabditis elegans development and behavior, encodes a clathrin-associated protein. Genes Dev 8, 60–73
    OpenUrlAbstract/FREE Full Text
    1. Levitan D. J.,
    2. Boyd L.,
    3. Mello C. C.,
    4. Kemphues K. J.,
    5. Stinchcomb D. T.
    (1994) par-2, a gene required for blastomere asymmetry in Caenorhabditis elegans, encodes zinc finger and ATP binding motifs. Proc. Natl. Acad. Sci. USA 91, 6108–6112
    OpenUrlAbstract/FREE Full Text
    1. Mello C. C.,
    2. Kramer J. M.,
    3. Stinchcomb D.,
    4. Ambros V.
    (1991) Efficient gene transfer in Caenorhabditis elegans: extrachromosomal maintenance and integration of transforming sequences. EMBO J 10, 3959–3970
    OpenUrlPubMedWeb of Science
    1. Mello C. C.,
    2. Schubert C.,
    3. Draper B.,
    4. Zhang W.,
    5. Lobel R.,
    6. Priess J. R.
    (1996) The PIE-1 protein and germline specification in C. elegans embryos. Nature 382, 710–712
    OpenUrlCrossRefPubMed
    1. Morton D. G.,
    2. Roos J. M.,
    3. Kemphues K. J.
    (1992) par-4, a gene required for cytoplasmic localization and determination of specific cell types in Caenorhabditis elegans embryogenesis. Genetics 130, 771–790
    OpenUrlAbstract/FREE Full Text
    1. Ponting C. P.,
    2. Phillips C.,
    3. Davies K. E.,
    4. Blake D. J.
    (1997) PDZ domain: targeting signalling molecules to sub-membranous sites. BioEssays 19, 469–479
    OpenUrlCrossRefPubMedWeb of Science
    1. Rocheleau C. E.,
    2. Downs W. D.,
    3. Lin R.,
    4. Wittmann C.,
    5. Bei Y.,
    6. Cha Y.-H.,
    7. Ali M.,
    8. Priess J.,
    9. Mello C.
    (1997) Wnt signaling and an APC-related gene specify endoderm in early C. elegans embryos. Cell 90, 707–717
    OpenUrlCrossRefPubMedWeb of Science
    1. Rosenzweig B.,
    2. Liao L. W.,
    3. Hirsh D.
    (1983) Sequence of the C. elegans transposable element Tc1. Nucleic Acid Res 11, 4201–4209
    OpenUrlAbstract/FREE Full Text
    1. Strome S.,
    2. Wood W. B.
    (1982) Immunofluorescence visualization of germ-line-specific cytoplasmic granules in embryos, larvae, and adults of Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 79, 1558–1562
    OpenUrlAbstract/FREE Full Text
    1. Sulston J.,
    2. Schierenberg E.,
    3. White J.,
    4. Thomson N.
    (1983) The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev. Biol 100, 67–119
    OpenUrl
    1. Tabuse Y.,
    2. Izumi Y.,
    3. Fabio P.,
    4. Kemphues K.,
    5. Miwa J.,
    6. Ohno S.
    (1998) Atypical protein kinase C is essential for generating early embryonic asymmetry in Caenorhabditis elegans. Development 125, 3607–3614
    OpenUrlAbstract
    1. Tenenhaus C.,
    2. Schubert C.,
    3. Seydoux G.
    (1998) Genetic requirements fror transcriptional silencing and PIE-1 localization in the embryonic germ lineage of C. elegans. Dev. Biol 15, 212–24
    1. Tsunoda J. S.,
    2. Sun Y.,
    3. Bodner R.,
    4. Suzuki E.,
    5. Becker A.,
    6. Socolich M.,
    7. Zuker C. S.
    (1997) A multivalent PDZ-domain protein assembles signalling complexes in a G-protein-coupled cascade. Nature 388, 243–249
    OpenUrlCrossRefPubMedWeb of Science
    1. Watts J. L.,
    2. Etemad-Moghadam B.,
    3. Guo S.,
    4. Boyd L.,
    5. Draper B. W.,
    6. Mello C. C.,
    7. Priess J. R.,
    8. Kemphues K. J.
    (1996) par-6, a gene involved in the establishment of asymmetry in early C. elegans embryos, mediates the asymmetric localization of PAR-3. Development 122, 3133–3140
    OpenUrlAbstract
    1. Wilson R.,
    2. Ainscough R.,
    3. Anderson K.,
    4. Baynes C.,
    5. Berks M.,
    6. Bonfield J.,
    7. Burton J.,
    8. Connell M.,
    9. Copsey T.,
    10. Cooper J.,
    11. et al.
    (1994). 2.2. Mb of contiguous nucleotide sequence from chromosome III of C. elegans. Nature 368, 32–38
    OpenUrlCrossRefPubMedWeb of Science
    1. Wu S.-L.,
    2. Saudinger J.,
    3. Olson E. N.,
    4. Rubin C. S.
    (1998) Structure, expression, and properties of an atypical protein kinase C (PKC-3) from Caenorhabdtis elegans. J. Biol.Chem 273, 1130–1143
    OpenUrlAbstract/FREE Full Text
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JOURNAL ARTICLES
PAR-6 is a conserved PDZ domain-containing protein that colocalizes with PAR-3 in Caenorhabditis elegans embryos
T.J. Hung, K.J. Kemphues
Development 1999 126: 127-135;
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