The cell polarity protein ASIP/PAR‐3 directly associates with junctional adhesion molecule (JAM)

The establishment and maintenance of cellular polarity are critical for the development of multicellular organisms. PAR (partitioning‐defective) proteins were identified in Caenorhabditis elegans as determinants of asymmetric cell division and polarized cell growth. Recently, vertebrate orthologues of two of these proteins, ASIP/PAR‐3 and PAR‐6, were found to form a signalling complex with the small GTPases Cdc42/Rac1 and with atypical protein kinase C (PKC). Here we show that ASIP/PAR‐3 associates with the tight‐junction‐associated protein junctional adhesion molecule (JAM) in vitro and in vivo. No binding was observed with claudin‐1, ‐4 or ‐5. In fibroblasts and CHO cells overexpressing JAM, endogenous ASIP is recruited to JAM at sites of cell–cell contact. Over expression of truncated JAM lacking the extracellular part disrupts ASIP/PAR‐3 localization at intercellular junctions and delays ASIP/PAR‐3 recruitment to newly formed cell junctions. During junction formation, JAM appears early in primordial forms of junctions. Our data suggest that the ASIP/PAR‐3–aPKC complex is tethered to tight junctions via its association with JAM, indicating a potential role for JAM in the generation of cell polarity in epithelial cells.

[1]  Y. Nagai,et al.  PAR‐6 regulates aPKC activity in a novel way and mediates cell‐cell contact‐induced formation of the epithelial junctional complex , 2001, Genes to cells : devoted to molecular & cellular mechanisms.

[2]  T. Ohnishi,et al.  Atypical Protein Kinase C Is Involved in the Evolutionarily Conserved Par Protein Complex and Plays a Critical Role in Establishing Epithelia-Specific Junctional Structures , 2001, The Journal of cell biology.

[3]  M. Aurrand-Lions,et al.  JAM-2, a Novel Immunoglobulin Superfamily Molecule, Expressed by Endothelial and Lymphatic Cells* , 2001, The Journal of Biological Chemistry.

[4]  R. Bjercke,et al.  A Novel Protein with Homology to the Junctional Adhesion Molecule , 2000, The Journal of Biological Chemistry.

[5]  E. Knust,et al.  Control of epithelial cell shape and polarity. , 2000, Current opinion in genetics & development.

[6]  E. Knust,et al.  Drosophila Atypical Protein Kinase C Associates with Bazooka and Controls Polarity of Epithelia and Neuroblasts , 2000, The Journal of cell biology.

[7]  P. Aspenström,et al.  The mammalian homologue of the Caenorhabditis elegans polarity protein PAR-6 is a binding partner for the Rho GTPases Cdc42 and Rac1. , 2000, Journal of cell science.

[8]  G. Pendl,et al.  Junctional adhesion molecule interacts with the PDZ domain-containing proteins AF-6 and ZO-1. , 2000, The Journal of biological chemistry.

[9]  Haigen Huang,et al.  Stimulation of erythropoiesis by inhibiting a new hematopoietic death receptor in transgenic zebrafish , 2000, Nature Cell Biology.

[10]  T. Pawson,et al.  A mammalian PAR-3–PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and cell polarity , 2000, Nature Cell Biology.

[11]  G. Joberty,et al.  The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42 , 2000, Nature Cell Biology.

[12]  F. Orsenigo,et al.  Interaction of Junctional Adhesion Molecule with the Tight Junction Components ZO-1, Cingulin, and Occludin* , 2000, The Journal of Biological Chemistry.

[13]  S. Walsh,et al.  Human junction adhesion molecule regulates tight junction resealing in epithelia. , 2000, Journal of cell science.

[14]  S. Hemmerich,et al.  Vascular Endothelial Junction-associated Molecule, a Novel Member of the Immunoglobulin Superfamily, Is Localized to Intercellular Boundaries of Endothelial Cells* , 2000, The Journal of Biological Chemistry.

[15]  A. Abo,et al.  A human homolog of the C. elegans polarity determinant Par-6 links Rac and Cdc42 to PKCζ signaling and cell transformation , 2000, Current Biology.

[16]  S. Tsukita,et al.  Pores in the Wall , 2000, The Journal of cell biology.

[17]  J. Knoblich,et al.  DmPAR-6 directs epithelial polarity and asymmetric cell division of neuroblasts in Drosophila , 2000, Nature Cell Biology.

[18]  M. Itoh,et al.  Direct Binding of Three Tight Junction-Associated Maguks, Zo-1, Zo-2, and Zo-3, with the Cooh Termini of Claudins , 1999, The Journal of cell biology.

[19]  E. Dejana,et al.  Leukocyte Recruitment in the Cerebrospinal Fluid of Mice with Experimental Meningitis Is Inhibited by an Antibody to Junctional Adhesion Molecule (Jam) , 1999, The Journal of experimental medicine.

[20]  James M. Anderson,et al.  Connexin-Occludin Chimeras Containing the Zo-Binding Domain of Occludin Localize at Mdck Tight Junctions and Nrk Cell Contacts , 1999, Journal of Cell Biology.

[21]  B. Bowerman,et al.  Cell polarity in the early Caenorhabditis elegans embryo. , 1999, Current opinion in genetics & development.

[22]  Marc D. H. Hansen,et al.  Cell polarity: Versatile scaffolds keep things in place , 1999, Current Biology.

[23]  M. Itoh,et al.  Differential behavior of E‐cadherin and occludin in their colocalization with ZO‐1 during the establishment of epithelial cell polarity , 1999, Journal of cellular physiology.

[24]  T. Pawson,et al.  The Carboxyl Terminus of B Class Ephrins Constitutes a PDZ Domain Binding Motif* , 1999, The Journal of Biological Chemistry.

[25]  K. Fujimoto,et al.  Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[26]  K. Kemphues,et al.  PAR-6 is a conserved PDZ domain-containing protein that colocalizes with PAR-3 in Caenorhabditis elegans embryos. , 1999, Development.

[27]  M. Aurrand-Lions,et al.  A novel immunoglobulin superfamily junctional molecule expressed by antigen presenting cells, endothelial cells and platelets. , 1998, Molecular immunology.

[28]  James M. Anderson,et al.  The Tight Junction Protein ZO-1 Establishes a Link between the Transmembrane Protein Occludin and the Actin Cytoskeleton* , 1998, The Journal of Biological Chemistry.

[29]  K. Kemphues,et al.  An Atypical PKC Directly Associates and Colocalizes at the Epithelial Tight Junction with ASIP, a Mammalian Homologue of Caenorhabditis elegans Polarity Protein PAR-3 , 1998, The Journal of cell biology.

[30]  F. Piano,et al.  Atypical protein kinase C cooperates with PAR-3 to establish embryonic polarity in Caenorhabditis elegans. , 1998, Development.

[31]  C. Renner,et al.  Structure of interleukin 16 resembles a PDZ domain with an occluded peptide binding site , 1998, Nature Structural &Molecular Biology.

[32]  E. Dejana,et al.  Junctional Adhesion Molecule, a Novel Member of the Immunoglobulin Superfamily That Distributes at Intercellular Junctions and Modulates Monocyte Transmigration , 1998, The Journal of cell biology.

[33]  Kazushi Fujimoto,et al.  Claudin-1 and -2: Novel Integral Membrane Proteins Localizing at Tight Junctions with No Sequence Similarity to Occludin , 1998, The Journal of cell biology.

[34]  J. Keane,et al.  Conservation of structure and function between human and murine IL-16. , 1998, Journal of immunology.

[35]  T. Noda,et al.  Occludin-deficient Embryonic Stem Cells Can Differentiate into Polarized Epithelial Cells Bearing Tight Junctions , 1998, The Journal of cell biology.

[36]  L. Gu,et al.  ZO-3, a Novel Member of the MAGUK Protein Family Found at the Tight Junction, Interacts with ZO-1 and Occludin , 1998, The Journal of cell biology.

[37]  C. V. Van Itallie,et al.  Occludin confers adhesiveness when expressed in fibroblasts. , 1997, Journal of cell science.

[38]  B. Gumbiner,et al.  A Synthetic Peptide Corresponding to the Extracellular Domain of Occludin Perturbs the Tight Junction Permeability Barrier , 1997, The Journal of cell biology.

[39]  K. Kemphues,et al.  par-6, a gene involved in the establishment of asymmetry in early C. elegans embryos, mediates the asymmetric localization of PAR-3. , 1996, Development.

[40]  R. Sternglanz,et al.  Identification of a new family of tissue-specific basic helix-loop-helix proteins with a two-hybrid system , 1995, Molecular and cellular biology.

[41]  M. Itoh,et al.  Cell-to-cell adherens junction formation and actin filament organization: similarities and differences between non-polarized fibroblasts and polarized epithelial cells. , 1995, Journal of cell science.

[42]  K. Suzuki,et al.  A new member of the third class in the protein kinase C family, PKC lambda, expressed dominantly in an undifferentiated mouse embryonal carcinoma cell line and also in many tissues and cells. , 1994, The Journal of biological chemistry.

[43]  M. Itoh,et al.  Occludin: a novel integral membrane protein localizing at tight junctions , 1993, The Journal of cell biology.

[44]  R. Blumenthal,et al.  Membrane asymmetry in epithelia: is the tight junction a barrier to diffusion in the plasma membrane? , 1981, Nature.