| Budget Amount *help |
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2003: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2002: ¥8,600,000 (Direct Cost: ¥8,600,000)
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| Research Abstract |
Multicellular organisms have various cell junctions and the structure termed a raft on the cell surface. These microdomains are composed of unique sets of proteins including receptors, cell adhesion molecules, cytoskeleton adaptor proteins, and signaling molecules. These components are organized as a functional complex through sequential protein-protein interactions. Because the disruption of cell junctions and other microdomains is implicated in various diseases, it is important to clarify how each protein is assembled into the complex.
We have studied a synaptic membrane-associated guanylate kinase (MAGUK) protein named S-SCAM. We previously reported that S-SCAM binds β-catenin. In this study, we have identified Axin, which regulates β-catenin degradation, as a binding partner of S-SCAM. We have also found that S-SCAM induces the synaptic accumulation of a cell adhesion molecule named neuroligin, and that neuroligin subsequently recruits another MAGUK protein, PSD-95, to synapses. Moreover, we have studied how SAPAP, a cytoskeleton adaptor protein that interacts with both of S-SCAM and PSD-95, is targeted to synapses.
A non-neuronal isoform of S-SCAM is named MIAGI-1 that is localized at tight junctions in epithelial cells. We have searched for MAGI-1-interacting proteins and discovered two novel molecules, JAM4 and Carom. JAM4 is a cell adhesion molecule that belongs to the immunoglobulin superfamily and involved in the regulation of paracellular permeability. Carom is a cytoskeleton adaptor protein. Carom binds to MAGI-1 in vitro. However, in polarized epithelial cells, Carom is not concentrated at tight junctions, is separate from MAGI-1, and interacts with CASK, which also belongs to MAGUK family of proteins. This finding suggests that protein-protein interactions are not stable but change during the establishment of cell polarity.
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