論文 - 詳細
| RRC ID | 46720 |
|---|---|
| 著者 | Ghosh-Roy A, Wu Z, Goncharov A, Jin Y, Chisholm AD. |
| タイトル | Calcium and cyclic AMP promote axonal regeneration in Caenorhabditis elegans and require DLK-1 kinase. |
| ジャーナル | J Neurosci |
| Abstract |
Axons of adult Caenorhabditis elegans neurons undergo robust regenerative growth after laser axotomy. Here we show that axotomy of PLM sensory neurons triggers axonal calcium waves whose amplitude correlates with the extent of regeneration. Genetic elevation of Ca(2+) or cAMP accelerates formation of a growth cone from the injured axon. Elevated Ca(2+) or cAMP also facilitates apparent fusion of axonal fragments and promotes branching to postsynaptic targets. Conversely, inhibition of voltage-gated calcium channels or calcium release from internal stores reduces regenerative growth. We identify the fusogen EFF-1 as critical for axon fragment fusion and the basic leucine zipper domain (bZip) protein CREB (cAMP response element-binding protein) as a key effector for branching. The effects of elevated Ca(2+) or cAMP on regrowth require the MAPKKK (mitogen-activated protein kinase kinase kinase) DLK-1. Increased cAMP signaling can partly bypass the requirement for the bZip protein CEBP-1, a downstream factor of the DLK-1 kinase cascade. These findings reveal the relationship between Ca(2+)/cAMP signaling and the DLK-1 MAPK (mitogen-activated protein kinase) cascade in regeneration. |
| 巻・号 | 30(9) |
| ページ | 3175-83 |
| 公開日 | 2010-3-3 |
| DOI | 10.1523/JNEUROSCI.5464-09.2010 |
| PII | 30/9/3175 |
| PMID | 20203177 |
| PMC | PMC2921707 |
| MeSH | Animals Axons / metabolism* Axotomy Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / metabolism* Calcium / metabolism* Calcium Channel Blockers / pharmacology Calcium Channels / drug effects Calcium Channels / metabolism Calcium Signaling / physiology Cyclic AMP / metabolism* Cyclic AMP Response Element-Binding Protein / metabolism Gene Expression Regulation / physiology Growth Cones / metabolism Lasers MAP Kinase Kinase Kinases / metabolism* MAP Kinase Signaling System / physiology Membrane Glycoproteins / metabolism Nerve Regeneration / physiology* Up-Regulation / physiology |
| IF | 5.674 |
| 引用数 | 155 |
| WOS 分野 | NEUROSCIENCES |
| リソース情報 | |
| 線虫 | tm2536 tm2214 tm2807 |