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Báo cáo khoa học: Characterization of the interactions of the nephrin intracellular domain Evidence that the scaffolding protein IQGAP1 associates with nephrin

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Nephrin is a signalling cell–cell adhesion protein of the Ig superfamily and the first identified component of the slit diaphragm that forms the critical and ultimate part of the glomerular ultrafiltration barrier. The extracellular domains of the nephrin molecules form a network of homophilic and heterophilic interactions building the structural scaffold of the slit dia-phragm between the podocyte foot processes. | iFEBS Journal Characterization of the interactions of the nephrin intracellular domain Evidence that the scaffolding protein IQGAP1 associates with nephrin Xiao Li Liu1 Pekka Kilpelainen1 Ulf Hellman3 Yi Sun1 Jorma Wartiovaara4 Ekaterina Morgunova1 Timo Pikkarainen1 Kunimasa Yan5 Anders P. Jonsson2 and Karl Tryggvason1 1 Divisions of Matrix Biology Department of MedicalBiochemistry and Biophysics Karolinska Institute Stockholm Sweden 2 MedicalChemistry Department of MedicalBiochemistry and Biophysics Karolinska Institute Stockholm Sweden 3 Ludwig Institute for Cancer Research Uppsala Sweden 4 Electron Microscopy Unit Institute of Biotechnology University of Helsinki Finland 5 Department of Pediatrics Kyorin University Schoolof Medicine Mitaka Tokyo Japan Keywords Fyn IQGAP1 phosphoinositide 3-kinase podocyte slit diaphragm Correspondence K. Tryggvason Karolinska Institutet Department of MedicalBiochemistry and Biophysics Division of Matrix Biology Scheeles Vag 2 B1 Plan 4 SE-17177 Stockholm Sweden Fax 46 8 316165 Tel 46 8 5248 7720 E-mail karl.tryggvason@mbb.ki.se Received 22 July 2004 revised 21 September 2004 accepted 22 September 2004 doi 10.1111 j.1432-1033.2004.04408.x Nephrin is a signalling cell-cell adhesion protein of the Ig superfamily and the first identified component of the slit diaphragm that forms the critical and ultimate part of the glomerular ultrafiltration barrier. The extracellular domains of the nephrin molecules form a network of homophilic and heterophilic interactions building the structural scaffold of the slit diaphragm between the podocyte foot processes. The intracellular domain of nephrin is connected indirectly to the actin cytoskeleton is tyrosine phosphorylated and mediates signalling from the slit diaphragm into the podocytes. CD2AP podocin Fyn kinase and phosphoinositide 3-kinase are reported intracellular interacting partners of nephrin although the biological roles of these interactions are unclarified. To characterize the .