Functional analyses of fibulin-4 on matrix assembly

2017 Fiscal Year Final Research Report

• Project/Area Number: 26461661
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Oita University
• Principal Investigator: Sasaki Takako 大分大学, 医学部, 助教 (30133193)
• Co-Investigator(Renkei-kenkyūsha): FUJIWARA Sakuhei 大分大学, 医学部, 教授 (90181411) ; UTANI Atsushi 長崎大学, 医学部, 教授 (10292707)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: 細胞外マトリックス / fibulin-4 / 変異 / 弾性線維 / アセンブリー

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.

Free Research Field

タンパク質化学