| Project/Area Number |
14207076
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (A)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Functional basic dentistry
|
|---|
| Research Institution | Tokyo Medical and Dental University |
|---|
Principal Investigator |
YANAGISHITA Masaki Tokyo Medical and Dental University, Graduate School, Biochemistry, Professor, 大学院・医歯学総合研究科, 教授 (70132793)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SHINOMURA Tamayuki Tokyo Medical and Dental University, Associate Professor, 大学院・医歯学総合研究科, 助教授 (70206118)
YOKOYAMA Miki Tokyo Medical and Dental University, Associate Professor, 大学院・医歯学総合研究科, 助教授 (70191533)
INOUE Katarzyna Anna Tokyo Medical and Dental University, Faculty of Dentistry, Educational Stuff, 歯学部, 教務職員 (90302877)
|
|---|
| Project Period (FY) |
2002 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥48,880,000 (Direct Cost: ¥37,600,000、Indirect Cost: ¥11,280,000)
Fiscal Year 2005: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2004: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2003: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2002: ¥22,360,000 (Direct Cost: ¥17,200,000、Indirect Cost: ¥5,160,000)
|
|---|
| Keywords | extracellular matrix / proteoglycan / heparan sulfate / membrane domain / molecular interactions / degrading enzyme / complex carbohydrates / ヘパラネース |
|---|
| Research Abstract |
In addition
to providing mechanical supports for various body structures in animals,
extracellular matrix also provides living environments for cells. Thus, it is involved in many crucial biological functions, including cell differentiation, proliferation, metabolism and regulated responses to environmental stimuli. Especially biological signals coming from outside cells are very important regulating fundamental cell functions. We have especially focused our attention on the analysis of molecular interactions between extracellular matrix molecules cellular molecules occurring at the cell surface, as a pertinent experimental system studying functional significance of extracellular matrix molecules. Specifically, a hypothesis that specialized plasma membrane domains are involved in the molecular interactions with extracellular matrix. A detergent-resistant plasma membrane preparation was made by solubilizing cell cultures with Triton X-100 followed by ultracentrifugation in a sucrose gradient. The presence of a specialized membrane domain was identified by colocalization of proteins, such as CD 38 and Lyn. A membrane domain preparation isolated from parathyroid cell sutures was examined by Western blot analyses probed with antibodies against heparan sulfate proteoglycans, which indicated significant enrichment syndecan-4 heparan sulfate proteoglycan and exclusion of syndecan-1. Further confirmation using MALDI-TOF mass spectroscopy has been on the way. Experiments also suggested that heparan sulfate proteoglycans participate in the structural stability of membrane domains. Effects of heparan sulfate degrading enzymes on the formation of membrane domains in the cell cultures in vitro are being studied. Future experiments will include detailed examination how heparan sulfate proteoglycans may be involved in the signal transduction and how they are contributing to the mechanical integrity of plasma membranes.
|
