| Project/Area Number |
12680646
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Functional biochemistry
|
|---|
| Research Institution | AICHI CANCER CENTER |
|---|
Principal Investigator |
NAGATA Koh-ichi Aichi Cancer Center, Div. Biochem., Section Head, 発がん制御研究部, 室長 (50252143)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
INAGAKI Masaki Aichi Cancer Center, Div. Biochem., Head, 発がん制御研究部, 部長 (30183007)
|
|---|
| Project Period (FY) |
2000 – 2001
|
| Project Status |
Completed (Fiscal Year 2001)
|
| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
|---|
| Keywords | Rho / RhoGEF / Neurite retraction / KIAA380 / Plexin B1 / 神経実起 / アクチン / グアニンヌクレオチド交換因子 |
|---|
| Research Abstract |
Semaphorins are repulsive guidance cues that regulate cell migration in vivo and in cultured neurons lead to growth cone collapse in vitro. Growth cone collapse is characterised by a disappearance offilopodial and lamellipodial actin structures in the growth cone. Small GTPases of the Rho family regulate the actin cytoskeleton in response to extracellular stimuli. Previously, we had found evidence for an effect ofa Rho-specific GEF, KIAA0380, on neurite retraction of neuronal culture cells, Neuro2A. Then we carried out yeast two hybrid screeing for binding partners of KIAA0380.
Consequently, we isolated plexin-B1 as a KIAA380-binding protein. By further analyses, we determined thatthe PDZ domain ofKIAA380 bind with the C terminus ofplexin B1. We next described that multimerisation of plexin-B1 led to activation of Rho, as observed by stress fiber formation. Interestingly a mutant KIAA0380 which lacks DH domain effectively inhibited the multimerization dependent Rho activation in Swiss 3T3 cells.
We decided to study furtherthe mechanism bywhich plexins cause collapse.
We present evidence foractivation of Rho by plexins via direct association with a Rho specific guanine nucleotide exchange factor (GEF), KIAA0380. The role of this RhoGEF in the growth cone collapse induced by semaphorins is currently being studied.
|
