論文 - 詳細
| RRC ID | 6538 |
|---|---|
| 著者 | Endo M, Ohashi K, Mizuno K. |
| タイトル | LIM kinase and slingshot are critical for neurite extension. |
| ジャーナル | J Biol Chem |
| Abstract |
Cofilin and its closely related protein, actin-depolymerizing factor (ADF), are key regulators of actin cytoskeleton dynamics that have been implicated in growth cone motility and neurite extension. Cofilin/ADF are inactivated by LIM kinase (LIMK)-catalyzed phosphorylation and reactivated by Slingshot (SSH)-catalyzed dephosphorylation. Here we examined the roles of cofilin/ADF, LIMKs (LIMK1 and LIMK2), and SSHs (SSH1 and SSH2) in nerve growth factor (NGF)-induced neurite extension. Knockdown of cofilin/ADF by RNA interference almost completely inhibited NGF-induced neurite extension from PC12 cells, and double knockdown of SSH1/SSH2 significantly suppressed both NGF-induced cofilin/ADF dephosphorylation and neurite extension from PC12 cells, thus indicating that cofilin/ADF and their activating phosphatases SSH1/SSH2 are critical for neurite extension. Interestingly, NGF stimulated the activities of both LIMK1 and LIMK2 in PC12 cells, and suppression of LIMK1/LIMK2 expression or activity significantly reduced NGF-induced neurite extension from PC12 cells or chick dorsal root ganglion (DRG) neurons. Inhibition of LIMK1/LIMK2 activity reduced actin filament assembly in the peripheral region of the growth cone of chick DRG neurons. These results suggest that proper regulation of cofilin/ADF activities through control of phosphorylation by LIMKs and SSHs is critical for neurite extension and that LIMKs regulate actin filament assembly at the tip of the growth cone. |
| 巻・号 | 282(18) |
| ページ | 13692-702 |
| 公開日 | 2007-5-4 |
| DOI | 10.1074/jbc.M610873200 |
| PII | S0021-9258(17)47447-3 |
| PMID | 17360713 |
| MeSH | Actin Cytoskeleton / metabolism Actin Depolymerizing Factors / genetics Actin Depolymerizing Factors / metabolism Actins / genetics Actins / metabolism Animals Chickens Destrin / genetics Destrin / metabolism Enzyme Activation / drug effects Enzyme Activation / physiology Ganglia, Spinal / cytology Ganglia, Spinal / enzymology Gene Expression Regulation, Enzymologic / drug effects Gene Expression Regulation, Enzymologic / physiology* Growth Cones / enzymology Lim Kinases Nerve Growth Factor / pharmacology Neurites / enzymology* PC12 Cells Phosphoprotein Phosphatases / genetics Phosphoprotein Phosphatases / metabolism* Phosphorylation / drug effects Protein Kinases / biosynthesis* Protein Kinases / genetics Protein Processing, Post-Translational / drug effects Protein Processing, Post-Translational / physiology* Rats |
| IF | 4.238 |
| 引用数 | 95 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | |