論文 - 詳細
| RRC ID | 10914 |
|---|---|
| 著者 | Bush JR, Wevrick R. |
| タイトル | Loss of Necdin impairs myosin activation and delays cell polarization. |
| ジャーナル | Genesis |
| Abstract |
NDN is one of several genes inactivated in Prader-Willi syndrome (PWS), a developmental disorder characterized by obesity, hypotonia, and developmental delay. We demonstrate that loss of Necdin in murine and human fibroblasts impairs polarity initiation through a Cdc42-myosin-dependent pathway, thereby reducing cell migration. We identified defective polarization in both primary neuron cultures and in the developing limb in Ndn-null mice. Ndn-null neurons fail to activate myosin light chain and display defective polarization with respect to a brain-derived neurotrophic factor gradient. Pax3+ muscle progenitors in Ndn-null developing forelimbs display defective polarization, do not adequately migrate into the dorsal limb bud, and extensor muscles are consequently smaller. These results provide strong evidence that Necdin is a key protein regulating polarization of the cytoskeleton during development. Furthermore, this is the first demonstration of a cellular defect in PWS and suggests a novel molecular mechanism to explain neurological and muscular pathophysiologies in PWS. |
| 巻・号 | 48(9) |
| ページ | 540-53 |
| 公開日 | 2010-9-1 |
| DOI | 10.1002/dvg.20658 |
| PMID | 20665884 |
| MeSH | Animals Cell Movement / physiology* Cell Polarity / physiology* Cytoskeleton / physiology* Fibroblasts Humans Immunoblotting Immunohistochemistry Limb Buds / physiology Mice Myosins / metabolism Nerve Tissue Proteins / deficiency* Nerve Tissue Proteins / metabolism Neurons / physiology Nuclear Proteins / deficiency* Nuclear Proteins / metabolism Phosphorylation Prader-Willi Syndrome / genetics Prader-Willi Syndrome / metabolism Prader-Willi Syndrome / physiopathology* Signal Transduction / genetics Signal Transduction / physiology* cdc42 GTP-Binding Protein / metabolism |
| IF | 1.76 |
| 引用数 | 11 |
| WOS 分野 | GENETICS & HEREDITY DEVELOPMENTAL 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 | PWS-Yamaguchi(RCB1560) |