| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Outline of Final Research Achievements |
Fibulin-4 is a 60kDa calcium binding glycoprotein that has an important role in development and integrity of extracellular matrices. Several mutations in the fibulin-4 gene are known in patients whose major symptoms are vascular abnormalities and cutis laxa. In order to elucidate the pathogenetic mechanisms, we expressed fibulin-4 mutants recombinantly in HEK293 cells, purified the proteins in native forms and analyzed alterations in secretion, matrix assembly, and interaction with other proteins. Our studies show that different mutations affect these properties in multiple ways, resulting in fibulin-4 deficiency and/or impaired ability to form elastic fibers. The substitution C267Y impaired secretion of the protein. The A397T mutation introduced an extra O-glycosylation site and deleted binding to LTBP1s. The binding of fibulin-4 to the LOX propeptide was strongly reduced by the mutation E57K. These findings show that different mutations result in different molecular defects.
|
