Membrane‐associated guanylate kinase with inverted orientation (MAGI)‐1/brain angiogenesis inhibitor 1‐associated protein (BAP1) as a scaffolding molecule for Rap small G protein GDP/GTP exchange protein at tight junctions

• Published in: Genes to cells : devoted to molecular & cellular mechanisms Vol. 5; no. 12; pp. 1009 - 1016
• Main Authors: Mino, Akihisa, Ohtsuka, Toshihisa, Inoue, Eiji, Takai, Yoshimi
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.12.2000
• Subjects: Adaptor Proteins, Signal Transducing; Amino Acid Motifs; Angiogenesis Inhibitors - metabolism; Animals; Brain - blood supply; Brain - metabolism; brain angiogenesis inhibitor 1-associated protein; Carrier Proteins - metabolism; Cell Adhesion Molecules, Neuronal - metabolism; Cell Line; COS Cells; GDP/GTP exchange protein; GTP-Binding Proteins - metabolism; Guanine Nucleotide Exchange Factors; Guanylate Kinases; Humans; MAGI-1 protein; Membrane Proteins; Membrane-associated guanylate kinase; Nerve Tissue Proteins - metabolism; neurone-specific synaptic scaffolding molecule; Nucleoside-Phosphate Kinase - metabolism; Protein Binding; Protein Structure, Tertiary; rap1 GTP-Binding Proteins - metabolism; Rap1 protein; SAP90-PSD95 Associated Proteins; Tight Junctions - metabolism
• ISSN: 1356-9597; 1365-2443
• DOI: 10.1046/j.1365-2443.2000.00385.x

Membrane‐associated guanylate kinase (MAGUK) with inverted orientation (MAGI)‐1/brain angiogenesis inhibitor 1‐associated protein (BAP1), is a member of the MAGUK family that has multiple PDZ domains and interacts with many transmembrane proteins, including receptors and channels, through these domains. MAGI‐1/BAP1 is ubiquitously expressed and localized at tight junctions in epithelial cells. It is an isoform of the neurone‐specific synaptic scaffolding molecule (S‐SCAM), which is known to interact with NMDA receptors and neuroligins. We have recently found that S‐SCAM also interacts with a signalling molecule, a GDP/GTP exchange protein (GEP) that is specific for Rap1 small G protein, Rap GEP, which has also recently been referred to as RA‐GEF/PDZ‐GEFI/CNras‐GEF. In this study, we have examined whether MAGI‐1/BAP1 also interacts with and serves as a scaffolding molecule for Rap GEP at tight junctions in epithelial cells. MAGI‐1/BAP1 similarly interacted with Rap GEP in cell‐free and intact cell systems. A Northern blot analysis revealed that Rap GEP was expressed in most tissues examined. However, neither postsynaptic density (PSD)‐95/synapse‐associated protein (SAP) 90 (another member of the MAGUK family) nor SAP97/human discs‐large tumour suppressor gene product (another ubiquitously expressed MAGUK localizing to adherens junctions in epithelial cells and the isoform of PSD‐95/SAP90) interacted with Rap GEP. These results indicate that MAGI‐1/BAP1 serves as a scaffolding molecule for Rap GEP at tight junctions in epithelial cells.