| RRC ID |
6536
|
| Author |
Kurita S, Gunji E, Ohashi K, Mizuno K.
|
| Title |
Actin filaments-stabilizing and -bundling activities of cofilin-phosphatase Slingshot-1.
|
| Journal |
Genes Cells
|
| Abstract |
Slingshot-1 (SSH1) is known to regulate actin filament dynamics by dephosphorylating and activating cofilin, an actin-depolymerizing factor. SSH1 binds to filamentous (F-) actin through its multiple F-actin-binding sites and its cofilin-phosphatase activity is enhanced by binding to F-actin. In this study, we demonstrate that SSH1 has F-actin-stabilizing and -bundling activities. In vitro actin depolymerization assays revealed that SSH1 suppressed spontaneous and cofilin-induced actin depolymerization in a dose-dependent manner. SSH1 inhibited F-actin binding and severing activities of cofilin. Low-speed centrifugation assays combined with fluorescence and electron microscopic analysis revealed that SSH1 has F-actin-bundling activity, independently of its cofilin-phosphatase activity. Deletion of N- or C-terminal regions of SSH1 significantly reduced its F-actin-stabilizing and -bundling activities, indicating that both regions are critical for these functions. As SSH1 does not form a homodimer, it probably bundles F-actin through its multiple F-actin-binding sites. Knockdown of SSH1 expression by RNA interference significantly suppressed stress fiber formation in C2C12 myoblast cells, indicating a role for SSH1 in stress fiber formation or stabilization in cells. SSH1 thus has the potential to regulate actin filament dynamics and organization in cells via F-actin-stabilizing and -bundling activities, in addition to its ability to dephosphorylate cofilin.
|
| Volume |
12(5)
|
| Pages |
663-76
|
| Published |
2007-5-1
|
| DOI |
10.1111/j.1365-2443.2007.01078.x
|
| PII |
GTC1078
|
| PMID |
17535256
|
| MeSH |
Actins / chemistry
Actins / metabolism*
Animals
Base Sequence
Binding Sites
Biopolymers / chemistry
Biopolymers / metabolism
Cell Line
Cofilin 2 / metabolism*
Dimerization
Drug Stability
Mice
Phosphoprotein Phosphatases / antagonists & inhibitors
Phosphoprotein Phosphatases / chemistry
Phosphoprotein Phosphatases / genetics
Phosphoprotein Phosphatases / metabolism*
Protein Structure, Quaternary
RNA Interference
RNA, Small Interfering / genetics
Stress Fibers / metabolism
|
| IF |
1.655
|
| Times Cited |
16
|
|
WOS Category
|
GENETICS & HEREDITY
CELL BIOLOGY
|
| Resource |
| Human and Animal Cells |
|
