1999 Fiscal Year Final Research Report Summary
Molecular and structural analyses of hemidesmosomes
| Project/Area Number |
09480192
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | Nagoya University |
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Principal Investigator |
OWARIBE Katsushi Nagoya Univ., Sch. of Informatics and Sci., Assoc. Prof., 情報文化学部, 助教授 (90109257)
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| Co-Investigator(Kenkyū-buntansha) |
USUKURA Jiro Nagoya Univ., Sch. of Med., and Sci., Assoc. Prof., 医学部, 助教授 (30143415)
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| Project Period (FY) |
1997 – 1999
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| Keywords | cell adhesion / hemidesmosome / bullous pemphigoid antigens / integrin α6β4 / HD1 / plectin |
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| Research Abstract |
The hemidesmosome (HD) is a cell-to-substrate adhesion apparatus found in stratified and complex epithelia. In this project, we have investigated molecular nature of major constituents of hemidesmosomes biochemically and structurally to characterize hemidesmosomal adhesion complex.
1. The rotary-shadowed images of purified BP180 showed a characteristic molecular shape consisting of three domains, a globular head, a central rod, and a flexible tail. Further, we demonstrated that the extracellular region of BP180 molecule was cleaved on the cell membrane and released from cell surface both in tissue and in culture. We suggested biological and clinical significance of this splitting.
We also demonstrated that when BP autoantibodies bound to BP180, the cells incorporated the immune complex, and suggested that this incorporation of BP180 results in defect of BP180 and causes blistering. In joint research projects, we reported revertant mosaicism in BP180-null patient caused by mitotic gene conversion and reliable prenatal diagnosis using fetal skin biopsy and monoclonal antibodies.
2. HD1 is a major HD constituent present in the most cytoplasmic side of HD plaques, and seems to play an important role in connecting adhesion molecules with keratin intermediate filaments. Using monoclonal antibodies, partial amino acid sequencing, partial cDNA sequencing and epitope mapping, together with the results from patients with EBS-MD, we identified HD1 as plectin, a versatile cross-linking protein. In joint research projects, we reported polarized expression of HD1 and interaction of HD1/plectin with integrin β4.
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