| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
Among the members of the cadherin gene superfamily, Fat protocadherin is unique in its molecular features as it is the largest cadherin and has 34 repeats of the extracellular cadherin-specific motif.fat has been known as a Drosophila tumor suppressor gene, and recent studies revealed that the Drosophila Fat regulates planar cell patterning. However, the biological function of mammalian Fat remains unknown. In this study, we investigated the properties of mammalian Fat1,a member of the vertebrate Fat sub family. We found that Fat1 was localized to filopodia and lamellipodia, and also to cell-cell contact sites in epithelial lines. Knock-down of Fat1 protein in PAM212 cells, a transformed keratinocyte line, resulted in elimination of actin fibers. Furthermore, we identified Ena/vasodilator-stimulated phosphoprotein(VASP) proteins as a binding partner of Fat1,and showed them as a downstream effecter of Fat1 to regulate actin polymerization. These results suggest a novel role of Fat1 to regulate actin cytoskeleton organization at cell peripheries and sites of cell contact.
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