| Project/Area Number |
11670021
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General anatomy (including Histology/Embryology)
|
|---|
| Research Institution | Juntendo University |
|---|
Principal Investigator |
KURIHARA Hidetake Juntendo University, School of Medicine, Associated Professor, 医学部, 助教授 (80311976)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SAKAI Tatsuo Juntendo University, School of Medicine, Professor, 医学部, 教授 (90114488)
|
|---|
| Project Period (FY) |
1999 – 2001
|
| Project Status |
Completed (Fiscal Year 2001)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
|---|
| Keywords | Kidney / Glomerulus / Podocyte / Slit membrane / Intercellular Junction |
|---|
| Research Abstract |
The foot processes of podocytes are held together by tenuous slit diaphragms which are continuous structure and serve as a fence to maintain distinctive apical and basal plasmalemmal domains on the podocytes. The molecular nature of slit diaphragm is still unknown. In this study our purpose is to identify the components of slit diaphragm and study on the relationship between intercellular junctions and slit diaphragms. Nephrin is identified as a product of the gene mutated in a patient with congenital nephritic syndrome of the Finnish type. We have cloned rat nephrin and identified it as the antigen of monoclonal antibody 5-1-6 which is specific for rat slit diaphragms. We have previously shown that the tight junction protein, ZO-1 locallizes along the cytoplasmic faces of slit diaphragm. These results suggest that the slit diaphragm is a modified tight junction. ACIP/PAR3 is located at the tight junction and plays a crucial role in the establishment of polarity in various cells. We have demonstrated that ACIP/PAR 3 is colocalized with ZO-1 in podocyte during differentiation and located at the base of slit diaphragm in the matured cell. Nephrin, a main component of slit diaphragm, was not associated with the tight junction between foot processes in developing and nephrotic glomeruli. Podocalyxin (apical membrane protein) and DPPIV (apical and basolateral membrane protein) were excluded from the junctional area. lt is still unknown what kind of proteins are involved in the junctional complex formation. We have identified that FAT, a novel member of the cadherin superfamily is a component of slit diaphragm in normal podocyte. This molecule is also associated with the junctional complex formation between foot processes in nephritic rat.
|
