| Project/Area Number |
10304065
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (A)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
動物生理・代謝
|
|---|
| Research Institution | CHIBA UNIVERSITY |
|---|
Principal Investigator |
OBINATA Takashi Chiba Univ. Dept. of Biology, Prof., 理学部, 教授 (40012413)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SATO Naruki Chiba Univ. Dept. of Biology, Assoc. Reseacher, 理学部, 助手 (40261896)
ABE Hiroshi Chiba Univ. Dept. of Biology, Assoc. Prof. Prof., 理学部, 助教授 (00222662)
|
|---|
| Project Period (FY) |
1998 – 2001
|
| Project Status |
Completed (Fiscal Year 2001)
|
| Budget Amount *help |
¥37,530,000 (Direct Cost: ¥35,700,000、Indirect Cost: ¥1,830,000)
Fiscal Year 2001: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Fiscal Year 2000: ¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1999: ¥8,500,000 (Direct Cost: ¥8,500,000)
Fiscal Year 1998: ¥15,400,000 (Direct Cost: ¥15,400,000)
|
|---|
| Keywords | myofibrillogenesis / C-protein / cofilin / actin / myosin / skeletal muscle / muscle development / muscular dystrophy / C-蛋白質 / ミオシン結合蛋白質 / ミオシン |
|---|
| Research Abstract |
We examined molecular mechanisms of morphogenesis and maintenance of myofibrils by mainly focussing on cofilin (CF), an actin-binding protein, and C-protein, a myosin- and connectin-bindirig protein. The results are summarized as follow :
1.Role of cofilin in myofibrillogenesis
1) Excess of CF in muscle cells, which was caused by cDNA transfection or injection of recombinant protein led to disruption of actin filaments and partial disorganization of myofibrils ; 2) In CF-deficient muscle cells, which were generated in mice by gene-manipulation, myofibrillar structures were severely damaged and muscle degeneration was induced in the region where CF-deficient muscle cells were concentrated ; 3) Inactivation of CF by increasing PIP2 in muscle cells also led to insufficient myofibril assembly.
Based on these results, we conclude that CF is important not only in myofibril formation but also in maintenance of normal muscle structure.
2. Molecular structure and function of C-protein
1) Molecular structures of mouse fast skeletal (F) and slow skeletal (S) C-proteins were determined by cDNA technology, and their expression and assembly were clarified and compared with that of cardiac isoform ; 2) Actin-binding domain was specified in N-terminal region of cardiac C-protein ; 3) A novel mouse cardiac C-protein was discovered, which slightly differ in the C-terminal myosin-binding and connectin-binding region and functionally weak. The expression of this variant is up-regulated in aged heart.
3. Role of actin-myosin interaction in myofibrillogenesis
We found that BDM (2,3-butanedione 2-monoxime), an inhibitor for myosin ATPase, suppresses, myfibrillogenesis and leads to myofibril disruption and thereby suggested that actin-myosin interaction plays a critical role in the early process of myofibrillogenesis.
|
