論文 - 詳細
| RRC ID | 70848 |
|---|---|
| 著者 | Pütz SM, Kram J, Rauh E, Kaiser S, Toews R, Lueningschroer-Wang Y, Rieger D, Raabe T. |
| タイトル | Loss of p21-activated kinase Mbt/PAK4 causes Parkinson-like phenotypes in Drosophila. |
| ジャーナル | Dis Model Mech |
| Abstract |
Parkinson's disease (PD) provokes bradykinesia, resting tremor, rigidity and postural instability, and also non-motor symptoms such as depression, anxiety, sleep and cognitive impairments. Similar phenotypes can be induced in Drosophila melanogaster through modification of PD-relevant genes or the administration of PD-inducing toxins. Recent studies correlated deregulation of human p21-activated kinase 4 (PAK4) with PD, leaving open the question of a causative relationship of mutations in this gene for manifestation of PD symptoms. To determine whether flies lacking the PAK4 homolog Mushroom bodies tiny (Mbt) show PD-like phenotypes, we tested for a variety of PD criteria. Here, we demonstrate that mbt mutant flies show PD-like phenotypes including age-dependent movement deficits, reduced life expectancy and fragmented sleep. They also react to a stressful situation with higher immobility, indicating an influence of Mbt on emotional behavior. Loss of Mbt function has a negative effect on the number of dopaminergic protocerebral anterior medial (PAM) neurons, most likely caused by a proliferation defect of neural progenitors. The age-dependent movement deficits are not accompanied by a corresponding further loss of PAM neurons. Previous studies highlighted the importance of a small PAM subgroup for age-dependent PD motor impairments. We show that impaired motor skills are caused by a lack of Mbt in this PAM subgroup. In addition, a broader re-expression of Mbt in PAM neurons improves life expectancy. Conversely, selective Mbt knockout in the same cells shortens lifespan. We conclude that mutations in Mbt/PAK4 can play a causative role in the development of PD phenotypes. |
| 巻・号 | 14(6) |
| 公開日 | 2021-6-1 |
| DOI | 10.1242/dmm.047811 |
| PII | 269133 |
| PMID | 34125184 |
| PMC | PMC8246267 |
| MeSH | Animals Drosophila / physiology Gene Knockdown Techniques Life Expectancy Motor Activity / genetics Neurons / physiology Parkinson Disease / genetics* Phenotype* Sleep / genetics p21-Activated Kinases / genetics* |
| IF | 4.651 |
| 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 | |
| ショウジョウバエ | DGRC#113956 |