Structure and function of "junctional adhesion molecules" (JAMs) expressed on platelets - characterisation of novel heterophilic interactions
Final Report Abstract
Junctional Adhesion Molecules (JAMs) belong to the immunoglobulin family of proteins, and they are expressed on a diverse range of cells, including endothelial cells, thrombocytes, and leukocytes. The JAM proteins regulate endothelial and epithelial „tight junctions“. The human homolog of JAM-A (hJAM-A), which is perhaps the best-known member of the family, serves as a ligand for the integrin LFA-1, and this interaction likely plays an important role in host inflammatory responses by mediating transmigration of leukocytes. Two hJAM-A homologs, hJAM-B and hJAM-C, were later identified, and shown to interact with integrins as well. JAMs can form homophilic and heterophilic interactions, and our project was aimed at establishing structures of JAM molecules and characterizing their homophilic and heterophilic interactions. Results obtained by the Langer group showed furthermore that the „extracellular matrix metalloproteinase inducer“ (EMMPRIN) is a new interaction partner for JAM-A, and we have therefore also undertaken efforts to characterize this interaction in more detail.
Publications
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Platelets contribute to the pathogenesis of experimental autoimmune encephalomyelitis. Circ Res. 2012 Apr 27;110(9):1202-10
Langer HF, Choi EY, Zhou H, Schleicher R, Chung KJ, Tang Z, Göbel K, Bdeir K, Chatzigeorgiou A, Wong C, Bhatia S, Kruhlak MJ, Rose JW, Burns JB, Hill KE, Qu H, Zhang Y, Lehrmann E, Becker KG, Wang Y, Simon DI, Nieswandt B, Lambris JD, Li X, Meuth SG, Kubes P, Chavakis T
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JAM-A associates with ZO-2, afadin, and PDZ- GEF1 to activate Rap2c and regulate epithelial barrier function. Mol Biol Cell. 2013 Sep;24(18):2849-60
Monteiro AC, Sumagin R, Rankin CR, Leoni G, Mina MJ, Reiter DM, Stehle T, Dermody TS, Schaefer SA, Hall RA, Nusrat A, Parkos CA
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Trans-dimerization of JAM-A regulates Rap2 and is mediated by a domain that is distinct from the cis-dimerization interface. Mol Biol Cell. 2014 May;25(10):1574-85
Monteiro AC, Luissint AC, Sumagin R, Lai C, Vielmuth F, Wolf MF, Laur O, Reiss K, Spindler V, Stehle T, Dermody TS, Nusrat A, Parkos CA
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Platelet bound oxLDL shows an inverse correlation with plasma anaphylatoxin C5a in patients with coronary artery disease. Platelets. 2016 Sep;27(6):593-597
Nording H, Giesser A, Patzelt J, Sauter R, Emschermann F, Stellos K, Gawaz M, Langer HF
