Rap guanine nucleotide exchange factor 2
PDZ domain binding
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.
<h4>Background</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>These results indicate that MAGI-1/BAP1 serves as a scaffolding molecule for Rap GEP at tight junctions in epithelial cells.