Migrating cells: JAM-A is localized at cellular protrusions and limits – but does not completely inhibit – the activities of Src and Rac1. Active Src and Rac1 act on Erk1/2, paxillin and the Wave complex to keep cell matrix interactions (CMA) dynamic and to promote protrusive activity. Contact-forming cells: JAM-A homophilic interactions result in JAM-A clustering at cell-cell contact sites. Enhanced recruitment of Csk by Tyr280-phosphorylated JAM-A leads to efficient inhibition of Src that is bound to αvβ5 integrin. Through its association with CD81, JAM-A also inhibits Rac1. Inhibition of Src and Rac1 results in inhibition of their downstream targets Erk1/2, paxillin, and the Wave complex. As a consequence, cells stabilize their interaction with the extracellular matrix at CMAs and downregulate their protrusive activity.

Volume 1 (Biological Role and Basic Mechanisms) identifies the molecular toolkit that is used to generate cell polarity, and it describes how this limited set of polarity molecules regulates various aspects of cell polarity in different cell types.

Volume 2 (Role in Development and Disease) puts a major emphasis on the physiological role of cell polarity. It describes the role of cell polarity during development and tumor formation, and it shows examples of how pathogens target cell polarity regulators for their own benefit.

A: Original Articles and Reviews

Groh AC, Möller-Kerutt A, Gilhaus K, Höffken V, Nedvetsky P, Kleimann S, Behrens M, Gosh S, Hansen U, Krahn MP, Ebnet K, Pavenstädt H, Ludwig A and Weide T (2024). PALS1 is a key regulator of the lateral distribution of tight junction proteins in renal epithelial cells. J Cell Sci. 137(5) jcs261303. doi: 10.1242/jcs261303.

Wibbe N and Ebnet K (2023). Cell Adhesion at the Tight Junctions: New Aspects and New Functions. Cells Nov 24;12(23):2701. doi: 10.3390/cells12232701.

Thüring EM*, Hartmann C*, Maddumage JC*, Javorsky A, Michels BE, Gerke V, Banks L, Humbert PO, Kvansakul M^ and Ebnet K^ (2023). Membrane recruitment of the cell polarity protein Scribble by the cell adhesion receptor TMIGD1. Commun Biol. Jul 10;6(1):702. doi: 10.1038/s42003-023-05088-3. (*equal contribution; ^shared corresponding authors).

Thüring EM, Hartmann C, Schwietzer YA and Ebnet K (2023). TMIGD1: Emerging functions of a tumor suppressor and adhesion receptor. Oncogene 42: 1777-1785.

Schwietzer MF, Thölmann S, Greune L and Ebnet K (2023). A micropattern-based assay to study contact inhibition of locomotion and entosis of adherent human and canine cells in vitro. STAR Protoc. Mar 22;4(2):102186. doi:10.1016/j.xpro.2023.102186.

Schwietzer MF*, Thölmann S*, Kummer D, Kaschler A, Greune L, Thüring EM, Schmidt MA, Gerke V and Ebnet K (2022). Loss of contact inhibition of locomotion in the absence of JAM-A promotes entotic cell engulfments. iScience. Sep 16;25(10):105144. doi:10.1016/j.isci.2022.105144. (*equal contribution).

Hartmann C*, Thüring EM*, Greune L, Michels BE, Pajonczyk D, Leußink S, Brinkmann F, Glaesner-Ebnet M, Wardelmann E, Zobel T, Schmidt MA, Janssen KP, Gerke V and Ebnet K (2022). Intestinal brush border formation requires a TMIGD1-based intermicrovillar adhesion complex. Sci Signal. Sep 13;15(751):eabm2449. doi: 10.1126/scisignal.abm2449. Epub 2022 Sep 13. (*equal contribution). 

Ebnet K and Gerke V (2022). Rho and Rab family small GTPases in the regulation of membrane polarity in epithelial cells. Front Cell Dev Biol. Jul 4;10:948013. doi: 10.3389/fcell.2022.948013.

Kummer D*, Steinbacher T*, Thölmann S*, Schwietzer MF, Hartmann C, Horenkamp S., Demuth S, Peddibhotla SSD, Brinkmann F, Kemper B, Schnekenburger J, Brandt M, Betz T, Liashkovich I, Koutel IU, Shahin V, Corvaia N, Rottner K, Tarbashevich K, Raz E, Greune L, Schmidt MA, Gerke V and Ebnet K (2022). A JAM-A – tetraspanin – αvβ5 integrin complex regulates contact inhibition of locomotion. J Cell Biol.221 Apr 4;221(4):e202105147. doi: 10.1083/jcb.202105147. Epub 2022 Mar 16. (*equal contribution).

Thölmann S, Seebach J, Otani T, Florin L, Schnittler H, Gerke V, Furuse M and Ebnet K (2022). JAM-A interacts with α3β1 integrin and tetraspanins CD151 and CD9 to regulate collective cell migration of polarized epithelial cells. Cell Mol Life Sci. Jan 24;79(2):88. doi: 10.1007/s00018-022-04140-5.

Haas AJ, Zihni C, Ruppel A, Hartmann C, Ebnet K, Tada M, Balda MS and Matter K (2020). Interplay between extracellular matrix stiffness and JAM-A regulates mechanical load on ZO-1 and tight junction assembly. Cell Rep. 32(3):107924. doi: 10.1016/j.celrep.2020.107924.

Hartmann C, Schwietzer YA, Kummer D, Kirschnick N, Hoppe E, Thüring EM, Glaesner-Ebnet M, Brinkmann F, Gerke V, Reuter S, Nakayama M and Ebnet K (2020). The mitochondrial outer membrane protein SYNJ2BP interacts with the cell adhesion molecule TMIGD1 and can recruit it to mitochondria. BMC Mol Cell Biol. 2020 Apr 17;21(1):30. doi: 10.1186/s12860-020-00274-1.

Kummer D,  Steinbacher T, Schwietzer MF, Thölmann S and Ebnet K (2020). Tetraspanins: Integrating cell surface receptors to functional microdomains in homeostasis and disease. Med Microbiol Immunol. 209(4)397-405. doi: 10.1007/s00430-020-00673-3.

Hartmann C, Schwietzer YA, Otani T, Furuse M and Ebnet K (2020). Physiological functions of Junctional Adhesion Molecules (JAMs) in tight junctions. BBA Biomembranes.1862(9):183299. doi: 10.1016/j.bbamem.2020.183299.

Otani T, Nguyen TP, Tokuda S, Sugihara K, Sugawara T, Furuse K, Miura T, Ebnet K and Furuse M (2019). Claudins and JAM-A coordinately regulate tight junction formation and epithelial polarity. J. Cell Biol. 218(10):3372-3396.

Merlen G, Kahale N, Ursic-Bedoya J, Bidault-Jourdainne V, Simerabet H, Doignon I, Tanfin Z, Garcin I, Péan N, Gautherot J, Davit-Spraul A, Guettier C, Humbert L, Rainteau D, Ebnet K, Ullmer C, Cassio D and Tordjmann T (2020). TGR5-dependent hepatoprotection through the regulation of biliary epithelium barrier function. Gut 69: 146-157.

Riddell M, Nakayama A, Hikita T, Mirzapourshafiyi F, Kawamura T, Pasha A, Li M, Masuzawa M, Looso M, Steinbacher T, Ebnet K, Potente M, Hirose T, Ohno S, Fleming I, Gattenlöhner S, Aung PP, Phung T, Yamasaki O, Yanagi T, Umemura H and Nakayama M.(2018). aPKC controls endothelial growth by modulating c-Myc via FoxO1 DNA binding ability. Nat Commun. 2018 Dec 17;9(1):5357. doi: 10.1038/s41467-018-07739-0.

Steinbacher T and Ebnet K (2018). The regulation of junctional actin dynamics by cell adhesion receptors. Histochem. Cell Biol. 150(4):341-350.

Kummer D  and Ebnet K (2018). Junctional Adhesion Molecules (JAMs): The JAM - Integrin connection. Cells. Mar 26;7(4). pii: E25. doi: 10.3390/cells7040025.

Steinbacher T, Kummer D  and Ebnet K (2018). Junctional Adhesion Molecule-A: Functional diversity through molecular promiscuity. Cell. Mol. Life Sci. 75: 1393–1409. doi: 10.1007/s00018-017-2729-0.

Ebnet K (2017). Junctional adhesion molecules (JAMs): Cell adhesion receptors with pleiotropic functions in cell physiology and development. Physiol. Rev. 97: 1529-1554. doi: 10.1152/physrev.00004.2017.

Ebnet K, Kummer D, Steinbacher T, Singh A, Nakayama M and Matis M (2018). Regulation of cell polarity by cell adhesion receptors. Sem. Cell Dev. Biol. 81: 2-12. doi:10.1016/j.semcdb.2017 .07.032.

Fededa JP, Esk C, Mierzwa B, Stanyte R, Yuan S, Zheng H, Ebnet K, Yan W, Knoblich JA and Gerlich DW (2016). MicroRNA-34/449 controls mitotic spindle orientation during mammalian cortex development. EMBO J. 35: 2386–2398.

Brinkmann BF, Steinbacher T, Hartmann C, Kummer D, Pajonczyk D, Mirzapourshafiyi F, Nakayama M, Weide T, Gerke V and Ebnet K (2016). VE-cadherin interacts with cell polarity protein Pals1 to regulate vascular lumen formation. Mol.Biol.Cell 27: 2811-2821.

Squarr AJ, Brinkmann K, Chen B, Steinbacher T, Ebnet K, Rosen MK and Bogdan S (2016). Fat2 acts through the WAVE regulatory complex to drive collective cell migration during tissue rotation. J Cell Biol. 212: 591-603.

Franz J, Brinkmann BF, König M, Hüve J, Stock C, Ebnet K and Riethmüller C (2016). Nanoscale imaging reveals a tetraspanin-CD9 coordinated elevation of endothelial ICAM-1 clusters. PLoS ONE 11(1):e0146598. doi: 10.1371/journal.pone.0146598.

Tuncay H and Ebnet K (2016). Cell adhesion molecule control of planar spindle orientation. Cell Mol Life Sci. 73(6):1195-207. doi: 10.1007/s00018-015-2116-7.

Tuncay H, Brinkmann BF and Ebnet K (2015). Mitotic spindle orientation: JAM-A can fix it. Cell Cycle 14(24): 3773-3774.

Schwickert A, Weghake E, Brüggemann K, Engbers A, Seggewiß J, Kemper B, Stock C, Brinkmann BF, Ebnet K, Kiesel L, Riethmüller C and Götte M (2015). microRNA miR-142-3p inhibits breast cancer cell invasiveness by synchronous targeting of WASL, integrin alpha V, and additional cytoskeletal elements. PLoS ONE 10(12): e0143993. doi:10.1371/journal.pone.0143993.

Tuncay H., Brinkmann BF, Steinbacher T, Schürmann A, Gerke V, Iden S and Ebnet K (2015). JAM-A regulates cortical dynein localization through Cdc42 to control planar spindle orientation during mitosis. Nat Commun. 2015 Aug 26;6:8128. doi: 10.1038/ncomms9128.

Peddibhotla S.S.D., Brinkmann BF, Kummer D, Tuncay H, Nakayama M, Adams R, Gerke V and Ebnet K (2013). Tetraspanin CD9 links junctional adhesion molecule-A to avb3 integrin to mediate bFGF-specific angiogenic signaling. Mol Biol Cell 24: 933-944.

Ebnet K (2013). JAM-A and aPKC: A close pair during cell-cell contact maturation and tight junction formation in epithelial cells. Tissue Barriers 1(1):e22993. doi: 10.4161/tisb.22993.

Iden* S, Misselwitz S*, Peddibhotla SSD, Tuncay H, Rehder D, Gerke V, Robenek H, Suzuki A and Ebnet K (2012). aPKC phosphorylates JAM-A at Ser285 to promote cell contact maturation and tight junction formation. J Cell Biol. 196: 623-639. (*equal contribution).

Stelzer S, Worlitzer MM, Bahnassawy L, Hemmer K, Rugani K, Werthschulte I, Schön AL, Brinkmann BF, Bunk EC, Palm T, Ebnet K and Schwamborn JC (2012). JAM-C is an apical surface marker for neural stem cells. Stem Cells Dev. 21: 757-766.

Fabritz L, Hoogendijk MG, Scicluna BP, van Amersfoorth SC, Fortmueller L, Wolf S, Laakmann S, Kreienkamp N, Piccini I, Breithardt G, Noppinger PR, Witt H, Ebnet K, Wichter T, Levkau B, Franke WW, Pieperhoff S, de Bakker JM, Coronel R and Kirchhof P (2011). Load-reducing therapy prevents development of arrhythmogenic right ventricular cardiomyopathy in plakoglobin-deficient mice. J Am Coll Cardiol.  57: 740-750.

Götte M, Mohr C, Koo C-Y, Stock C, Vaske A-K, Viola M, Ibrahim SA, Peddibhotla S, Teng YH-F, Low J-Y, Ebnet K, Kiesel L and Yip GW (2010). miR-145-dependent targeting of Junctional Adhesion Molecule A and modulation of fascin expression are associated with reduced breast cancer cell motility and invasiveness. Oncogene  29: 6569-6580.

Stelzer S, Ebnet K and Schwamborn JC (2010). JAM-A is a novel surface marker for NG2-Glia in the adult mouse brain. BMC Neurosci. 11: 27, 1-9.

Ebnet K (2008). Organization of multiprotein complexes at cell-cell junctions. Histochem Cell Biol. 130: 1-20.

Ebnet K, Iden S, Gerke V and Suzuki A (2008). Regulation of epithelial and endothelial junctions by PAR proteins. Front. Biosci. 13: 6520-6536.
Pardo J, Wallich R, Ebnet K, Iden S, Zentgraf H, Martin P, Ekiciler A, Prins A, Müllbacher A, Huber M and Simon MM (2007). Granzyme B is expressed in mouse mast cells in vivo and in vitro and causes delayed cell death independent of perforin. Cell Death Differ. 14: 1768-1779.

Mandicourt G, Iden S, Ebnet K, Aurrand-Lions M and Imhof BA (2007). JAM-C regulates tight junctions and integrin-mediated cell adhesion and migration. J Biol Chem. 282: 1830-1837.

Iden S, Rehder D, August B, Suzuki A, Wolburg-Buchholz K, Wolburg H, Ohno S, Behrens J, Vestweber D and Ebnet K (2006). A distinct PAR complex associates physically with VE-cadherin in vertebrate endothelial cells. EMBO Rep. 7: 1239-1246.

Rehder D, Iden S, Nasdala I, Wegener J, Meyer Zu Brickwedde MK, Vestweber D and Ebnet K (2006). Junctional adhesion molecule-A participates in the formation of apico-basal polarity through different domains. Exp Cell Res. 312: 3389-3403.

Kondrashov AV, Kiefmann M, Ebnet K, Khanam T, Muddashetty RS and Brosius J (2005). Inhibitory effect of naked neural BC1 RNA or BC200 RNA on eukaryotic in vitro translation systems is reversed by poly(A)-binding protein (PABP). J Mol Biol. 353: 88-103.

Baumeister U, Funke R, Ebnet K, Vorschmitt H, Koch S and Vestweber D (2005). Association of Csk to VE-cadherin and inhibition of cell proliferation. EMBO J. 24: 1686-1695.

Wegmann F, Ebnet K, Du Pasquier L, Vestweber D and Butz S (2004). Endothelial adhesion molecule ESAM binds directly to the multidomain adaptor MAGI-1 and recruits it to cell contacts. Exp Cell Res. 300: 121-133.

Gliki G, Ebnet K, Aurrand-Lions M, Imhof BA and Adams RH (2004) Spermatid differentiation requires the assembly of a cell polarity complex downstream of junctional adhesion molecule-C. Nature 431: 320-324.

Ebnet K, Suzuki A, Ohno S and Vestweber D (2004). Junctional adhesion molecules (JAMs): More molecules with dual functions? J Cell Sci. 117: 19-29.

Ebnet K, Aurrand-Lions M, Kuhn A, Kiefer F, Butz S, Zander K, Meyer Zu Brickwedde MK, Suzuki A, Imhof BA and Vestweber D (2003). The junctional adhesion molecule (JAM) family members JAM-2 and JAM-3 associate with the cell polarity protein PAR-3: A possible role for JAMs in endothelial cell polarity. J Cell Sci. 116: 3879-3891.

Suzuki A, Ishiyama C, Hashiba K, Shimizu M, Ebnet K and Ohno S (2002). aPKC kinase activity is required for the asymmetric differentiation of the premature junctional complex during epithelial cell polarization. J Cell Sci. 115: 3565-3573.

Nasdala I, Wolburg-Buchholz K, Wolburg H, Kuhn A, Ebnet K, Brachtendorf B, Samulowitz U, Kuster B, Engelhardt B, Vestweber D and Butz S (2002). A transmembrane tight junction protein selectively expressed on endothelial cells and platelets. J Biol Chem. 277: 16294-16303.

Ebnet K, Suzuki A, Horikoshi Y, Hirose T, Meyer Zu Brickwedde MK, Ohno S and Vestweber D (2001). The cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion molecule (JAM). EMBO J. 20: 3738-3748.

Ebnet K, Schulz CU, Meyer Zu Brickwedde MK, Pendl GG and Vestweber D (2000). Junctional adhesion molecule interacts with the PDZ domain-containing proteins AF-6 and ZO-1. J Biol Chem. 275: 27979-27988.

Ebnet K and Vestweber D (1999). Molecular mechanisms that control leukocyte extravasation: the selectins and the chemokines. Histochem Cell Biol. 112: 1-23.

Simon MM, Hausmann M, Tran T, Ebnet K, Tschopp J, Hla RT and Mullbacher A (1997). In vitro- and ex vivo-derived cytolytic leukocytes from granzyme A x B double knockout mice are defective in granule-mediated apoptosis but not lysis of target cells. J Exp Med. 186: 1781-1786.

Ebnet K, Brown KD, Siebenlist UK, Simon MM and Shaw S (1997). Borrelia burgdorferi activates nuclear factor-kappa B and is a potent inducer of chemokine and adhesion molecule gene expression in endothelial cells and fibroblasts. J Immunol. 158: 3285-3292.

Ebnet K, Simon MM and Shaw S (1996). Regulation of chemokine gene expression in human endothelial cells by proinflammatory cytokines and Borrelia burgdorferi. Ann NY Acad. Sci. 797: 107-117.

Mullbacher A, Ebnet K, Blanden RV, Hla RT, Stehle T, Museteanu C and Simon MM (1996). Granzyme A is critical for recovery of mice from infection with the natural cytopathic viral pathogen, ectromelia. Proc Natl Acad Sci. USA 93: 5783-5787.

Ebnet K, Kaldjian EP, Anderson AO and Shaw S (1996). Orchestrated information transfer underlying leukocyte endothelial interactions. Annu Rev Immunol. 14: 155-177.

Ebnet K, Hausmann M, Lehmann-Grube F, Mullbacher A, Kopf M, Lamers M and Simon MM (1995). Granzyme A-deficient mice retain potent cell-mediated cytotoxicity. EMBO J. 14: 4230-4239.

Ebnet K, Levelt CN, Tran TT, Eichmann K and Simon MM (1995). Transcription of granzyme A and B genes is differentially regulated during lymphoid ontogeny. J Exp Med. 181: 755-763.

Dick T, Reichmann G, Ebnet K, Simon MM, Dienes HP, Echternacher B, Krammer PH and Reske-Kunz AB (1993). An ovalbumin peptide-specific cytotoxic T cell clone with antigen self-presentation capacity uses two distinct mechanisms to kill target cells. Cell Immunol. 152: 333-347.

Ebnet K, Kramer MD and Simon MM (1992). Organization of the gene encoding the mouse T-cell-specific serine proteinase "granzyme A". Genomics 13: 502-508.

Ebnet K, Chluba-de Tapia J, Hurtenbach U, Kramer MD and Simon MM (1991). In vivo primed mouse T cells selectively express T cell-specific serine proteinase-1 and the proteinase-like molecules granzyme B and C. Int Immunol. 3: 9-19.

Kramer MD, Moter SE, Simon MM, Ebnet K and Wallich R (1990). Polymerase chain reaction in the demonstration of Borrelia burgdorferi DNA. Hautarzt 41: 587-590.

Wallich R, Moter SE, Simon MM, Ebnet K, Heiberger A and Kramer MD (1990). The Borrelia burgdorferi flagellum-associated 41-kilodalton antigen (flagellin): molecular cloning, expression, and amplification of the gene. Infect Immun. 58: 1711-1719.
 

B: Book Chapters

Brinkmann BF, Tuncay H and Ebnet K (2015). Homotypic cell-cell interactions and apico-basal polarity in epithelial cells and endothelial cells. In “Cell Polarity 1: Biological role and basic mechanisms”. Ed. K. Ebnet, Springer International Publishing AG Switzerland, pp. 277-302

Ebnet K, Brinkmann BF, Kummer D, Misselwitz S, Peddibhotla SSD and Tuncay H (2013). Tight junctions, Junctional Adhesion Molecules (JAMs), and the Blood Brain Barrier. In "Tight Junctions in Cancer Metastasis", Cancer Metastasis - Biology and Treatment 19. Ed. T.A. Martin and W.G. Jiang , Springer, Dordrecht-Heidelberg-New York-London, pp. 119-129.

Ebnet K, Gerke V and Iden S (2010). Cadherins and the regulation of tight junctions and cell polarity. In "Molecular and Functional Diversities of Cadherin and Protocadherin". Ed. K. Yoshida, Research Signpost, Kerala, India, pp. 57-68.

Ebnet K, V. Gerke and M. Aurrand-Lions (2010). Junctional Adhesion Molecules (JAMs). In "Modern Insights Into Disease From Molecules to Man. Adhesion Molecules". Ed. Victor R Preedy, Science Publishers, Enfield, USA, pp. 37-51.

Wolburg H, Lippoldt A and Ebnet K (2007). Tight junctions in the blood-brain barrier. In "Handbook of Neurochemistry and Molecular Neurobiology". Ed. A. Lajtha, Vol. 11: "Neural Membranes and Transport". Ed. M.E.A. Reith, Springer Berlin-Heidelberg, pp. 4-27.

Wolburg H, Lippoldt A and Ebnet K (2006). Tight junctions and the blood-brain barrier. In "Selected topics on tight junctions". Eds. L. Mariscal, RG Landes Bioscience, Georgetown, TX, USA, pp. 175-195.

Simon MM, Ebnet K, Gires O, Museteanu C, Siebers A, Stehle T, Tran TT, Zhong W, Gern L, Kramer MD and Wallich R (1997). Lyme Borreliosis: progress in the development of a vaccine and new insights into the pathogenesis of the disease. In "Emerging and Re-Emerging Diseases Transmitted by Arthropod Vectors and Rodents; Proceedings of the 2nd Int. Symposium on Lyme Disease" in Japan". Eds. Y. Yanagihara and T. Masuzawa, pp. 245-259.

Sarin A, Ebnet K, Zacharchuk CM and Henkart PA (1997). Caspase inhibitors as molecular probes of cell death. In "Programmed Cell Death: Proceedings of the 1996 International Symposium on Programmed Cell Death" in Shanghai. Eds. Y.B. Shi, Y. Shi, D.W. Scott, and Y. Xu, Plenum Press, New York, pp. 51-62.

Kramer MD, Vettel U, Ebnet K and Simon MM (1993). The murine T cell-specific serine proteinase-1: cleavage activity on synthetic and natural substrates. In "Cytotoxic Cells: Recognition, Effector Function, Generation, and Methods", chapter 59, p. 516-520. Eds. M. Sitkovsky and P. Henkart, Birkhäuser, Boston.#

Simon MM, Ebnet K and Kramer MD (1993). Molecular analysis and possible pleiotropic function(s) of the T cell-specific serine proteinase-1 (TSP-1). In "Cytotoxic Cells: Recognition, Effector Function, Generation, and Methods", chapter. 26, p. 278-294. Eds. M. Sitkovsky and P. Henkart, Birkhäuser, Boston.
 

C: Additional Publications

Vestweber D and Ebnet K (2001). Leukozyteneinwanderung in entzündete Gewebe – wie kommen die Abwehrzellen zum Wirkungsort? Biologen heute 25: 1-5.

Ebnet K (1999). Immunüberwachung und Entzündung – ein komplexes Wechselspiel zwischen Leukozyten und Endothelzellen. Biologie in unserer Zeit 29: 26-35.