Afdn

Summary

Gene Symbol: Afdn
Description: afadin, adherens junction formation factor
Alias: 5033403D15Rik, AF6, Af-6, Afadin, Gm314, I-afadin, Mllt4, S-afadin, afadin, myeloid/lymphoid or mixed lineage-leukemia translocation to 4 homolog, myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 4, myeloid/lymphoid or mixed-lineage leukemia; translocated to, 4, protein Af-6
Species: mouse
Products:     Afdn

Top Publications

  1. Ikeda W, Nakanishi H, Miyoshi J, Mandai K, Ishizaki H, Tanaka M, et al. Afadin: A key molecule essential for structural organization of cell-cell junctions of polarized epithelia during embryogenesis. J Cell Biol. 1999;146:1117-32 pubmed
    b>Afadin is an actin filament-binding protein that binds to nectin, an immunoglobulin-like cell adhesion molecule, and is colocalized with nectin at cadherin-based cell-cell adherens junctions (AJs)...
  2. Yamamoto H, Maruo T, Majima T, Ishizaki H, Tanaka Okamoto M, Miyoshi J, et al. Genetic deletion of afadin causes hydrocephalus by destruction of adherens junctions in radial glial and ependymal cells in the midbrain. PLoS ONE. 2013;8:e80356 pubmed publisher
    ..The major cell-cell adhesion molecules at AJs are cadherins and nectins. Afadin binds to both nectins and ?-catenin and recruits the cadherin-?-catenin complex to the nectin-based cell-cell ..
  3. Majima T, Takeuchi K, Sano K, Hirashima M, Zankov D, Tanaka Okamoto M, et al. An Adaptor Molecule Afadin Regulates Lymphangiogenesis by Modulating RhoA Activity in the Developing Mouse Embryo. PLoS ONE. 2013;8:e68134 pubmed publisher
    b>Afadin is an intracellular binding partner of nectins, cell-cell adhesion molecules, and plays important roles in the formation of cell-cell junctions...
  4. Beaudoin G, Schofield C, Nuwal T, Zang K, Ullian E, Huang B, et al. Afadin, a Ras/Rap effector that controls cadherin function, promotes spine and excitatory synapse density in the hippocampus. J Neurosci. 2012;32:99-110 pubmed publisher
    ..b>Afadin is a Rap-regulated, actin-binding protein that promotes cadherin complex assembly as well as binding many other ..
  5. Fukumoto Y, Kurita S, Takai Y, Ogita H. Role of scaffold protein afadin dilute domain-interacting protein (ADIP) in platelet-derived growth factor-induced cell movement by activating Rac protein through Vav2 protein. J Biol Chem. 2011;286:43537-48 pubmed publisher
    ..We show here that the scaffold protein afadin dilute domain-interacting protein (ADIP), an afadin-binding protein, is involved in the regulation of cell ..
  6. Komura H, Ogita H, Ikeda W, Mizoguchi A, Miyoshi J, Takai Y. Establishment of cell polarity by afadin during the formation of embryoid bodies. Genes Cells. 2008;13:79-90 pubmed publisher
    b>Afadin directly links nectin, an immunoglobulin-like cell-cell adhesion molecule, to actin filaments (F-actin) at adherens junctions (AJs)...
  7. Majima T, Ogita H, Yamada T, Amano H, Togashi H, Sakisaka T, et al. Involvement of afadin in the formation and remodeling of synapses in the hippocampus. Biochem Biophys Res Commun. 2009;385:539-44 pubmed publisher
    ..Components of both the nectin-afadin and cadherin-catenin cell adhesion systems exclusively accumulate at PAJs...
  8. Miyata M, Rikitake Y, Takahashi M, Nagamatsu Y, Yamauchi Y, Ogita H, et al. Regulation by afadin of cyclical activation and inactivation of Rap1, Rac1, and RhoA small G proteins at leading edges of moving NIH3T3 cells. J Biol Chem. 2009;284:24595-609 pubmed publisher
    ..We showed here that knockdown of afadin, an actin-binding protein, in NIH3T3 cells resulted in a failure to develop leading edge structures in association ..
  9. Gil Sanz C, Landeira B, Ramos C, Costa M, M ller U. Proliferative defects and formation of a double cortex in mice lacking Mltt4 and Cdh2 in the dorsal telencephalon. J Neurosci. 2014;34:10475-87 pubmed publisher
    ..Here we show that the adherens junction proteins afadin and CDH2 are critical for the control of cell proliferation in the dorsal telencephalon and for the formation of ..
  10. Radziwill G, Weiss A, Heinrich J, Baumgartner M, Boisguerin P, Owada K, et al. Regulation of c-Src by binding to the PDZ domain of AF-6. EMBO J. 2007;26:2633-44 pubmed
    ..c-Src is recruited by AF-6 to cell-cell contact sites, suggesting that c-Src is regulated by a PDZ protein in special cellular locations. We identified a novel type of c-Src regulation by interaction with a PDZ protein. ..

Detail Information

Publications70

  1. Ikeda W, Nakanishi H, Miyoshi J, Mandai K, Ishizaki H, Tanaka M, et al. Afadin: A key molecule essential for structural organization of cell-cell junctions of polarized epithelia during embryogenesis. J Cell Biol. 1999;146:1117-32 pubmed
    b>Afadin is an actin filament-binding protein that binds to nectin, an immunoglobulin-like cell adhesion molecule, and is colocalized with nectin at cadherin-based cell-cell adherens junctions (AJs)...
  2. Yamamoto H, Maruo T, Majima T, Ishizaki H, Tanaka Okamoto M, Miyoshi J, et al. Genetic deletion of afadin causes hydrocephalus by destruction of adherens junctions in radial glial and ependymal cells in the midbrain. PLoS ONE. 2013;8:e80356 pubmed publisher
    ..The major cell-cell adhesion molecules at AJs are cadherins and nectins. Afadin binds to both nectins and ?-catenin and recruits the cadherin-?-catenin complex to the nectin-based cell-cell ..
  3. Majima T, Takeuchi K, Sano K, Hirashima M, Zankov D, Tanaka Okamoto M, et al. An Adaptor Molecule Afadin Regulates Lymphangiogenesis by Modulating RhoA Activity in the Developing Mouse Embryo. PLoS ONE. 2013;8:e68134 pubmed publisher
    b>Afadin is an intracellular binding partner of nectins, cell-cell adhesion molecules, and plays important roles in the formation of cell-cell junctions...
  4. Beaudoin G, Schofield C, Nuwal T, Zang K, Ullian E, Huang B, et al. Afadin, a Ras/Rap effector that controls cadherin function, promotes spine and excitatory synapse density in the hippocampus. J Neurosci. 2012;32:99-110 pubmed publisher
    ..b>Afadin is a Rap-regulated, actin-binding protein that promotes cadherin complex assembly as well as binding many other ..
  5. Fukumoto Y, Kurita S, Takai Y, Ogita H. Role of scaffold protein afadin dilute domain-interacting protein (ADIP) in platelet-derived growth factor-induced cell movement by activating Rac protein through Vav2 protein. J Biol Chem. 2011;286:43537-48 pubmed publisher
    ..We show here that the scaffold protein afadin dilute domain-interacting protein (ADIP), an afadin-binding protein, is involved in the regulation of cell ..
  6. Komura H, Ogita H, Ikeda W, Mizoguchi A, Miyoshi J, Takai Y. Establishment of cell polarity by afadin during the formation of embryoid bodies. Genes Cells. 2008;13:79-90 pubmed publisher
    b>Afadin directly links nectin, an immunoglobulin-like cell-cell adhesion molecule, to actin filaments (F-actin) at adherens junctions (AJs)...
  7. Majima T, Ogita H, Yamada T, Amano H, Togashi H, Sakisaka T, et al. Involvement of afadin in the formation and remodeling of synapses in the hippocampus. Biochem Biophys Res Commun. 2009;385:539-44 pubmed publisher
    ..Components of both the nectin-afadin and cadherin-catenin cell adhesion systems exclusively accumulate at PAJs...
  8. Miyata M, Rikitake Y, Takahashi M, Nagamatsu Y, Yamauchi Y, Ogita H, et al. Regulation by afadin of cyclical activation and inactivation of Rap1, Rac1, and RhoA small G proteins at leading edges of moving NIH3T3 cells. J Biol Chem. 2009;284:24595-609 pubmed publisher
    ..We showed here that knockdown of afadin, an actin-binding protein, in NIH3T3 cells resulted in a failure to develop leading edge structures in association ..
  9. Gil Sanz C, Landeira B, Ramos C, Costa M, M ller U. Proliferative defects and formation of a double cortex in mice lacking Mltt4 and Cdh2 in the dorsal telencephalon. J Neurosci. 2014;34:10475-87 pubmed publisher
    ..Here we show that the adherens junction proteins afadin and CDH2 are critical for the control of cell proliferation in the dorsal telencephalon and for the formation of ..
  10. Radziwill G, Weiss A, Heinrich J, Baumgartner M, Boisguerin P, Owada K, et al. Regulation of c-Src by binding to the PDZ domain of AF-6. EMBO J. 2007;26:2633-44 pubmed
    ..c-Src is recruited by AF-6 to cell-cell contact sites, suggesting that c-Src is regulated by a PDZ protein in special cellular locations. We identified a novel type of c-Src regulation by interaction with a PDZ protein. ..
  11. Inagaki M, Irie K, Ishizaki H, Tanaka Okamoto M, Morimoto K, Inoue E, et al. Roles of cell-adhesion molecules nectin 1 and nectin 3 in ciliary body development. Development. 2005;132:1525-37 pubmed
  12. Lim S, Lim K, Giuliano R, Federoff H. Temporal and spatial localization of nectin-1 and l-afadin during synaptogenesis in hippocampal neurons. J Comp Neurol. 2008;507:1228-44 pubmed publisher
    Nectins are cell adhesion molecules that, together with the intracellular binding partner afadin, mediate adhesion and signaling at a variety of intercellular junctions...
  13. Kanzaki N, Ogita H, Komura H, Ozaki M, Sakamoto Y, Majima T, et al. Involvement of the nectin-afadin complex in PDGF-induced cell survival. J Cell Sci. 2008;121:2008-17 pubmed publisher
    The nectin-afadin complex is involved in the formation of cell-cell junctions, such as adherens junctions (AJs) and tight junctions (TJs)...
  14. Tawa H, Rikitake Y, Takahashi M, Amano H, Miyata M, Satomi Kobayashi S, et al. Role of afadin in vascular endothelial growth factor- and sphingosine 1-phosphate-induced angiogenesis. Circ Res. 2010;106:1731-42 pubmed publisher
    ..However, little is known about the effectors of Rap1 involved in angiogenesis. It is not known whether afadin, an adherens junction protein that connects immunoglobulin-like adhesion molecule nectins to the actin ..
  15. Kurita S, Ogita H, Takai Y. Cooperative role of nectin-nectin and nectin-afadin interactions in formation of nectin-based cell-cell adhesion. J Biol Chem. 2011;286:36297-303 pubmed publisher
    The nectin cell adhesion molecules interact in trans with each other through their extracellular regions and with afadin through their cytoplasmic tails, forming adherens junctions in cooperation with cadherins...
  16. Yang Z, Zimmerman S, BRAKEMAN P, Beaudoin G, Reichardt L, MARCIANO D. De novo lumen formation and elongation in the developing nephron: a central role for afadin in apical polarity. Development. 2013;140:1774-84 pubmed publisher
    ..We demonstrate that lumen formation and elongation require afadin, a nectin adaptor protein implicated in adherens junction formation...
  17. Miyata M, Ogita H, Komura H, Nakata S, Okamoto R, Ozaki M, et al. Localization of nectin-free afadin at the leading edge and its involvement in directional cell movement induced by platelet-derived growth factor. J Cell Sci. 2009;122:4319-29 pubmed publisher
    b>Afadin is an actin-filament-binding protein that binds to nectin, an immunoglobulin-like cell-cell adhesion molecule, and plays an important role in the formation of adherens junctions...
  18. Fournier G, Cabaud O, Josselin E, Chaix A, Adelaide J, Isnardon D, et al. Loss of AF6/afadin, a marker of poor outcome in breast cancer, induces cell migration, invasiveness and tumor growth. Oncogene. 2011;30:3862-74 pubmed publisher
    b>Afadin/AF6, an F-actin-binding protein, is ubiquitously expressed in epithelia and has a key role during development, through its regulatory role in cell-cell junction organization...
  19. Takahashi K, Nakanishi H, Miyahara M, Mandai K, Satoh K, Satoh A, et al. Nectin/PRR: an immunoglobulin-like cell adhesion molecule recruited to cadherin-based adherens junctions through interaction with Afadin, a PDZ domain-containing protein. J Cell Biol. 1999;145:539-49 pubmed
    We have isolated a novel actin filament-binding protein, named afadin, localized at cadherin-based cell-cell adherens junctions (AJs) in various tissues and cell lines...
  20. Halford M, Armes J, Buchert M, Meskenaite V, Grail D, Hibbs M, et al. Ryk-deficient mice exhibit craniofacial defects associated with perturbed Eph receptor crosstalk. Nat Genet. 2000;25:414-8 pubmed
    ..biochemical data implicate Ryk in signalling mediated by Eph receptors and the cell-junction-associated Af-6 (also known as Afadin). Our findings highlight the importance of signal crosstalk between members of different RTK subfamilies.
  21. Hock B, Böhme B, Karn T, Yamamoto T, Kaibuchi K, Holtrich U, et al. PDZ-domain-mediated interaction of the Eph-related receptor tyrosine kinase EphB3 and the ras-binding protein AF6 depends on the kinase activity of the receptor. Proc Natl Acad Sci U S A. 1998;95:9779-84 pubmed
    ..the Eph-related RTKs EphA7, EphB2, EphB3, EphB5, and EphB6 interact with the PDZ domain of the ras-binding protein AF6. A mutational analysis revealed that six C-terminal residues of the receptors are involved in binding to the PDZ ..
  22. Zhadanov A, Provance D, Speer C, Coffin J, Goss D, Blixt J, et al. Absence of the tight junctional protein AF-6 disrupts epithelial cell-cell junctions and cell polarity during mouse development. Curr Biol. 1999;9:880-8 pubmed
    ..In the mouse, AF-6 is encoded by the Af6 gene...
  23. Tanaka Okamoto M, Hori K, Ishizaki H, Itoh Y, Onishi S, Yonemura S, et al. Involvement of afadin in barrier function and homeostasis of mouse intestinal epithelia. J Cell Sci. 2011;124:2231-40 pubmed publisher
    b>Afadin interacts with the cytoplasmic region of nectins, which are immunoglobulin-like cell adhesion molecules at adherens junctions, and links them to the actin cytoskeleton...
  24. Asada M, Irie K, Morimoto K, Yamada A, Ikeda W, Takeuchi M, et al. ADIP, a novel Afadin- and alpha-actinin-binding protein localized at cell-cell adherens junctions. J Biol Chem. 2003;278:4103-11 pubmed
    b>Afadin is an actin filament (F-actin)-binding protein that is associated with the cytoplasmic tail of nectin, a Ca(2+)-independent immunoglobulin-like cell-cell adhesion molecule...
  25. Kurita S, Yamada T, Rikitsu E, Ikeda W, Takai Y. Binding between the junctional proteins afadin and PLEKHA7 and implication in the formation of adherens junction in epithelial cells. J Biol Chem. 2013;288:29356-68 pubmed publisher
    ..cadherin and nectin and their associating cytoplasmic proteins including ?-catenin, ?-catenin, p120(ctn), and afadin. Our series of studies have revealed that nectin first forms cell-cell adhesion and then recruits cadherin to form ..
  26. Sai K, Wang S, Kaito A, Fujiwara T, Maruo T, Itoh Y, et al. Multiple roles of afadin in the ultrastructural morphogenesis of mouse hippocampal mossy fiber synapses. J Comp Neurol. 2017;525:2719-2734 pubmed publisher
    ..Here, we electron microscopically analyzed the ultrastructure of this synapse in afadin-deficient mice...
  27. Okabe N, Ozaki Kuroda K, Nakanishi H, Shimizu K, Takai Y. Expression patterns of nectins and afadin during epithelial remodeling in the mouse embryo. Dev Dyn. 2004;230:174-86 pubmed
    ..are Ca2+-independent immunoglobulin-like cell adhesion molecules connected to the actin cytoskeleton through afadin. Nectins play roles in a variety of cell-cell junctions in cooperation with or independently of cadherins...
  28. LIEDTKE M, Ayton P, Somervaille T, Smith K, Cleary M. Self-association mediated by the Ras association 1 domain of AF6 activates the oncogenic potential of MLL-AF6. Blood. 2010;116:63-70 pubmed publisher
    ..The MLL-AF6 fusion gene represents the most common leukemogenic fusion of mixed lineage leukemia (MLL) to a cytoplasmic partner ..
  29. Takito J, Nakamura M, Yoda M, Tohmonda T, Uchikawa S, Horiuchi K, et al. The transient appearance of zipper-like actin superstructures during the fusion of osteoclasts. J Cell Sci. 2012;125:662-72 pubmed publisher
    ..Understanding of the zipper-like structure might lead to selective therapeutics for bone diseases caused by hypermultinucleated osteoclasts. ..
  30. Kanai Azuma M, Mattick J, Kaibuchi K, Wood S. Co-localization of FAM and AF-6, the mammalian homologues of Drosophila faf and canoe, in mouse eye development. Mech Dev. 2000;91:383-6 pubmed
    ..Expression is not limited to the epithelia however, as FAM and AF-6 also co-localize during lens fibre development as well as in sub-populations of the neural retina. ..
  31. Yano T, Matsui T, Tamura A, Uji M, Tsukita S. The association of microtubules with tight junctions is promoted by cingulin phosphorylation by AMPK. J Cell Biol. 2013;203:605-14 pubmed publisher
    ..These findings collectively suggest that the regulated cingulin-MT association has a specific role in TJ-related epithelial morphogenesis that is sensitive to metabolic homeostasis-related AMPK activity. ..
  32. Johnson H, Hanson L, Chen Y, Bieber A, Buono R, Ferraro T, et al. Quantitative trait loci analysis reveals candidate genes implicated in regulating functional deficit and CNS vascular permeability in CD8 T cell-initiated blood-brain barrier disruption. BMC Genomics. 2013;14:678 pubmed publisher
    ..These genes encode for factors that may be potential targets for therapeutic approaches to treat disorders characterized by CD8 T cell-mediated BBB disruption. ..
  33. Mora J, Fenwick M, Castle L, Baithun M, Ryder T, Mobberley M, et al. Characterization and significance of adhesion and junction-related proteins in mouse ovarian follicles. Biol Reprod. 2012;86:153, 1-14 pubmed publisher
    ..Lack of classic markers suggests that GCs are not epithelial. Identification of AJs during GC cuboidalization highlights the importance of AJs in regulating initiation of follicle growth. ..
  34. Yoshida T, Iwata T, Takai Y, Birchmeier W, Yamato M, Okano T. Afadin requirement for cytokine expressions in keratinocytes during chemically induced inflammation in mice. Genes Cells. 2014;19:842-52 pubmed publisher
    b>Afadin is a filamentous actin-binding protein and a mediator of nectin signaling. Nectins are Ig-like cell adhesion molecules, and the nectin family is composed of four members, nectin-1 to nectin-4...
  35. Fujiwara Y, Goda N, Tamashiro T, Narita H, Satomura K, Tenno T, et al. Crystal structure of afadin PDZ domain-nectin-3 complex shows the structural plasticity of the ligand-binding site. Protein Sci. 2015;24:376-85 pubmed publisher
    b>Afadin, a scaffold protein localized in adherens junctions (AJs), links nectins to the actin cytoskeleton. Nectins are the major cell adhesion molecules of AJs...
  36. Ishiuchi T, Takeichi M. Nectins localize Willin to cell-cell junctions. Genes Cells. 2012;17:387-97 pubmed publisher
    ..In addition, we report that the positioning of nectins at the AJC is dependent on their binding to afadin. Thus, our results suggest that the nectin-afadin interaction plays a role in the correct localization of Willin.
  37. Miyata M, Maruo T, Kaito A, Wang S, Yamamoto H, Fujiwara T, et al. Roles of afadin in the formation of the cellular architecture of the mouse hippocampus and dentate gyrus. Mol Cell Neurosci. 2017;79:34-44 pubmed publisher
    ..We previously showed that the cell adhesion molecules nectins and its binding protein afadin play roles in the formation of the mossy fiber synapses which are formed between the mossy fibers of the dentate ..
  38. Azizoglu D, Braitsch C, MARCIANO D, Cleaver O. Afadin and RhoA control pancreatic endocrine mass via lumen morphogenesis. Genes Dev. 2017;31:2376-2390 pubmed publisher
    ..We show that loss of the scaffolding protein Afadin disrupts de novo lumenogenesis and lumen continuity in the tip epithelium...
  39. Deshpande A, Chen L, Fazio M, Sinha A, Bernt K, Banka D, et al. Leukemic transformation by the MLL-AF6 fusion oncogene requires the H3K79 methyltransferase Dot1l. Blood. 2013;121:2533-41 pubmed publisher
    ..In this study, we demonstrate that MLL-AF6 requires continued activity of the histone-methyltransferase DOT1L to maintain expression of the MLL-AF6-driven ..
  40. Li X, Lynn B, Nagy J. The effector and scaffolding proteins AF6 and MUPP1 interact with connexin36 and localize at gap junctions that form electrical synapses in rodent brain. Eur J Neurosci. 2012;35:166-81 pubmed publisher
    ..Here, we demonstrate that two proteins known to be associated with tight and adherens junctions, namely AF6 and MUPP1, are components of neuronal gap junctions in rodent brain...
  41. Manabe N, Hirai S, Imai F, Nakanishi H, Takai Y, Ohno S. Association of ASIP/mPAR-3 with adherens junctions of mouse neuroepithelial cells. Dev Dyn. 2002;225:61-9 pubmed
    ..on tight junctions in cultured epithelial cells, it localizes on adherens junctions outlined by beta-catenin and afadin at the luminal surface, an apical end of the neuroepithelium in developing mouse central nervous systems...
  42. Sato T, Kanai Y, Noma T, Kanai Azuma M, Taya S, Matsui T, et al. A close correlation in the expression patterns of Af-6 and Usp9x in Sertoli and granulosa cells of mouse testis and ovary. Reproduction. 2004;128:583-94 pubmed
    ..It further suggests that the post-translational regulation of Af-6 by Usp9x may be one potential pathway to control the cell adhesion dynamics in mammalian gametogenesis. ..
  43. Pantaleon M, Kanai Azuma M, Mattick J, Kaibuchi K, Kaye P, Wood S. FAM deubiquitylating enzyme is essential for preimplantation mouse embryo development. Mech Dev. 2001;109:151-60 pubmed
    ..However, the nascent protein was mislocalised at the apical surface of blastomeres. Therefore FAM is required for preimplantation mouse embryo development and regulates beta-catenin and AF-6 in vivo. ..
  44. Rakotomamonjy J, Brunner M, Jüschke C, Zang K, Huang E, Reichardt L, et al. Afadin controls cell polarization and mitotic spindle orientation in developing cortical radial glia. Neural Dev. 2017;12:7 pubmed publisher
    ..Conditional deletion of Afadin, a protein required for formation and maintenance of epithelial tissues, leads to abnormalities in radial glial ..
  45. Okabe N, Shimizu K, Ozaki Kuroda K, Nakanishi H, Morimoto K, Takeuchi M, et al. Contacts between the commissural axons and the floor plate cells are mediated by nectins. Dev Biol. 2004;273:244-56 pubmed
    ..These results indicate that the contacts between the commissural axons and the floor plate cells are mediated by the hetero-trans-interaction between nectin-1 and -3 and involved in regulation of the trajectory of the commissural axons. ..
  46. Gil Sanz C, Franco S, Martinez Garay I, Espinosa A, Harkins Perry S, Muller U. Cajal-Retzius cells instruct neuronal migration by coincidence signaling between secreted and contact-dependent guidance cues. Neuron. 2013;79:461-77 pubmed publisher
    ..Furthermore, reelin signaling to Rap1 promotes neuronal Cdh2 function via nectin3 and afadin, thus directing the broadly expressed homophilic cell adhesion molecule Cdh2 toward mediating heterotypic cell-..
  47. Katsuno T, Umeda K, Matsui T, Hata M, Tamura A, Itoh M, et al. Deficiency of zonula occludens-1 causes embryonic lethal phenotype associated with defected yolk sac angiogenesis and apoptosis of embryonic cells. Mol Biol Cell. 2008;19:2465-75 pubmed publisher
    ..In conclusion, ZO-1 may be functionally important for cell remodeling and tissue organization in both the embryonic and extraembryonic regions, thus playing an essential role in embryonic development...
  48. Takekuni K, Ikeda W, Fujito T, Morimoto K, Takeuchi M, Monden M, et al. Direct binding of cell polarity protein PAR-3 to cell-cell adhesion molecule nectin at neuroepithelial cells of developing mouse. J Biol Chem. 2003;278:5497-500 pubmed
    ..Nectins are associated with the actin cytoskeleton through afadin, of which the PDZ domain binds to nectins through their C-terminal four amino acids...
  49. Tanaka Okamoto M, Itoh Y, Miyoshi J, Mizoguchi A, Mizutani K, Takai Y, et al. Genetic ablation of afadin causes mislocalization and deformation of Paneth cells in the mouse small intestinal epithelium. PLoS ONE. 2014;9:e110549 pubmed publisher
    b>Afadin is an actin filament-binding protein that acts cooperatively in cell adhesion with the cell adhesion molecule nectin, and in directional cell movement with the small G protein Rap1 in a nectin-independent manner...
  50. Nojima H, Adachi M, Matsui T, Okawa K, Tsukita S, Tsukita S. IQGAP3 regulates cell proliferation through the Ras/ERK signalling cascade. Nat Cell Biol. 2008;10:971-8 pubmed publisher
    ..Thus, IQGAP3 regulates the promotion of cell proliferation through Ras-dependent ERK activation. ..
  51. Kobayashi R, Kurita S, Miyata M, Maruo T, Mandai K, Rikitake Y, et al. s-Afadin binds more preferentially to the cell adhesion molecules nectins than l-afadin. Genes Cells. 2014;19:853-63 pubmed publisher
    l-Afadin was originally purified from rat brain as an actin filament (F-actin)-binding protein that was homologous to the AF-6 gene product...
  52. Nakata S, Fujita N, Kitagawa Y, Okamoto R, Ogita H, Takai Y. Regulation of platelet-derived growth factor receptor activation by afadin through SHP-2: implications for cellular morphology. J Biol Chem. 2007;282:37815-25 pubmed
    ..Here, we showed a novel role of afadin in the regulation of PDGF-induced intracellular signaling and cellular morphology in NIH3T3 cells...
  53. Maeta K, Edamatsu H, Nishihara K, Ikutomo J, Bilasy S, Kataoka T. Crucial Role of Rapgef2 and Rapgef6, a Family of Guanine Nucleotide Exchange Factors for Rap1 Small GTPase, in Formation of Apical Surface Adherens Junctions and Neural Progenitor Development in the Mouse Cerebral Cortex. Eneuro. 2016;3: pubmed publisher
    ..These results demonstrate a cell-autonomous role of the Rapgef2/6-Rap1 pathway in maintaining the apical surface AJ structures, which is necessary for the proper development of neural progenitor cells. ..
  54. Yamamoto H, Mandai K, Konno D, Maruo T, Matsuzaki F, Takai Y. Impairment of radial glial scaffold-dependent neuronal migration and formation of double cortex by genetic ablation of afadin. Brain Res. 2015;1620:139-52 pubmed publisher
    ..b>Afadin, a membrane scaffolding protein, regulates the formation of adherens junctions (AJs) and cell migration to form ..
  55. Tanaka Y, Nakanishi H, Kakunaga S, Okabe N, Kawakatsu T, Shimizu K, et al. Role of nectin in formation of E-cadherin-based adherens junctions in keratinocytes: analysis with the N-cadherin dominant negative mutant. Mol Biol Cell. 2003;14:1597-609 pubmed
    ..adhesion molecule at AJs and is associated with E-cadherin through their respective peripheral membrane proteins, afadin and catenins, which connect nectin and cadherin to the actin cytoskeleton, respectively...
  56. Fukuda T, Kominami K, Wang S, Togashi H, Hirata K, Mizoguchi A, et al. Aberrant cochlear hair cell attachments caused by Nectin-3 deficiency result in hair bundle abnormalities. Development. 2014;141:399-409 pubmed publisher
    ..These results indicate that, owing to the loss of Nectin-3, hair cells contact each other inappropriately and form abnormal junctions, ultimately resulting in abnormal hair bundle orientation and morphology. ..
  57. Daane J, Enders A, Downs K. Mesothelium of the murine allantois exhibits distinct regional properties. J Morphol. 2011;272:536-56 pubmed publisher
    ..for protein synthesis than did the distal squamous mesothelium; however, at most stages, VCM exhibited robust afadin (AF-6), whereas the DCM uniquely contained alpha-4-integrin...
  58. Koike C, Nishida A, Akimoto K, Nakaya M, Noda T, Ohno S, et al. Function of atypical protein kinase C lambda in differentiating photoreceptors is required for proper lamination of mouse retina. J Neurosci. 2005;25:10290-8 pubmed
    ..Our data suggest that properly polarized photoreceptors anchor progenitors at the apical edge of the neural retina, which may be essential for building correct laminar organization of the retina. ..
  59. Lim S, Chang A, Giuliano R, Federoff H. Ectodomain shedding of nectin-1 regulates the maintenance of dendritic spine density. J Neurochem. 2012;120:741-51 pubmed publisher
    ..Expression of these mutants significantly alters the density of dendritic spines. These findings suggest that ectodomain shedding of nectin-1 regulates dendritic spine density and related synaptic functions. ..
  60. Toyoshima D, Mandai K, Maruo T, Supriyanto I, Togashi H, Inoue T, et al. Afadin regulates puncta adherentia junction formation and presynaptic differentiation in hippocampal neurons. PLoS ONE. 2014;9:e89763 pubmed publisher
    ..b>Afadin and its binding cell adhesion molecules, nectin-1 and nectin-3, together with N-cadherin, are concentrated at ..
  61. Quilliam L, Castro A, Rogers Graham K, Martin C, Der C, Bi C. M-Ras/R-Ras3, a transforming ras protein regulated by Sos1, GRF1, and p120 Ras GTPase-activating protein, interacts with the putative Ras effector AF6. J Biol Chem. 1999;274:23850-7 pubmed
    ..Although M-Ras coimmunoprecipitated with AF6, a putative regulator of cell junction formation, overexpression of AF6 did not contribute to fibroblast ..
  62. Monteiro A, Sumagin R, Rankin C, Leoni G, Mina M, Reiter D, et al. JAM-A associates with ZO-2, afadin, and PDZ-GEF1 to activate Rap2c and regulate epithelial barrier function. Mol Biol Cell. 2013;24:2849-60 pubmed publisher
    ..Here we report that JAM-A associates directly with ZO-2 and indirectly with afadin, and this complex, along with PDZ-GEF1, activates the small GTPase Rap2c...
  63. Shah B, Lutter D, Tsytsyura Y, Glyvuk N, Sakakibara A, Klingauf J, et al. Rap1 GTPases Are Master Regulators of Neural Cell Polarity in the Developing Neocortex. Cereb Cortex. 2017;27:1253-1269 pubmed publisher
    ..Taken together, the loss of RGC and neuronal polarity results in the disruption of cortical organization. ..
  64. Lachke S, Higgins A, Inagaki M, Saadi I, Xi Q, Long M, et al. The cell adhesion gene PVRL3 is associated with congenital ocular defects. Hum Genet. 2012;131:235-50 pubmed publisher
    ..Collectively, these data identify PVRL3 as a critical gene involved in a Nectin-mediated cell-cell adhesion mechanism in human ocular development. ..
  65. Gao L, Yang Z, Hiremath C, Zimmerman S, Long B, BRAKEMAN P, et al. Afadin orients cell division to position the tubule lumen in developing renal tubules. Development. 2017;144:3511-3520 pubmed publisher
    ..We recently found that the F-actin-binding protein afadin is required for lumen continuity in developing renal tubules, though its mechanism of action remains unknown...
  66. Satoh Horikawa K, Nakanishi H, Takahashi K, Miyahara M, Nishimura M, Tachibana K, et al. Nectin-3, a new member of immunoglobulin-like cell adhesion molecules that shows homophilic and heterophilic cell-cell adhesion activities. J Biol Chem. 2000;275:10291-9 pubmed
    ..This system consists of at least nectin, a Ca(2+)-independent immunoglobulin-like adhesion molecule, and afadin, an actin filament-binding protein, that connects nectin to the actin cytoskeleton...
  67. Shingai T, Ikeda W, Kakunaga S, Morimoto K, Takekuni K, Itoh S, et al. Implications of nectin-like molecule-2/IGSF4/RA175/SgIGSF/TSLC1/SynCAM1 in cell-cell adhesion and transmembrane protein localization in epithelial cells. J Biol Chem. 2003;278:35421-7 pubmed
    ..Nectins bind afadin, whereas Necl-2 did not bind afadin but bound Pals2, a membrane-associated guanylate kinase family member known to ..
  68. Yamada T, Kuramitsu K, Rikitsu E, Kurita S, Ikeda W, Takai Y. Nectin and junctional adhesion molecule are critical cell adhesion molecules for the apico-basal alignment of adherens and tight junctions in epithelial cells. Genes Cells. 2013;18:985-98 pubmed publisher
    ..We describe the cooperative roles of these CAMs and CPMs in the apico-basal alignment of TJs and AJs in epithelial cells. ..
  69. Iwasawa N, Negishi M, Oinuma I. R-Ras controls axon branching through afadin in cortical neurons. Mol Biol Cell. 2012;23:2793-804 pubmed publisher
    ..Here we identify afadin, an actin-binding protein harboring Ras association (RA) domains, as an effector of R-Ras inducing axon branching ..
  70. Geng X, Maruo T, Mandai K, Supriyanto I, Miyata M, Sakakibara S, et al. Roles of afadin in functional differentiations of hippocampal mossy fiber synapse. Genes Cells. 2017;22:715-722 pubmed publisher
    ..and serial block face-scanning electron microscopy that atypical puncta adherentia junctions are formed in the afadin-deficient mossy fiber synapse and that the complexity of postsynaptic spines and mossy fiber boutons, the number ..