論文 - 詳細
| RRC ID | 57169 |
|---|---|
| 著者 | Azuma Y, Tokuda T, Kushimura Y, Yamamoto I, Mizuta I, Mizuno T, Nakagawa M, Ueyama M, Nagai Y, Iwasaki Y, Yoshida M, Pan D, Yoshida H, Yamaguchi M. |
| タイトル | Hippo, Drosophila MST, is a novel modifier of motor neuron degeneration induced by knockdown of Caz, Drosophila FUS. |
| ジャーナル | Exp Cell Res |
| Abstract |
Mutations in the Fused in Sarcoma (FUS) gene have been identified in familial ALS in human. Drosophila contains a single ortholog of human FUS called Cabeza (Caz). We previously established Drosophila models of ALS targeted to Caz, which developed the locomotive dysfunction and caused anatomical defects in presynaptic terminals of motoneurons. Accumulating evidence suggests that ALS and cancer share defects in many cellular processes. The Hippo pathway was originally discovered in Drosophila and plays a role as a tumor suppressor in mammals. We aimed to determine whether Hippo pathway genes modify the ALS phenotype using Caz knockdown flies. We found a genetic link between Caz and Hippo (hpo), the Drosophila ortholog of human Mammalian sterile 20-like kinase (MST) 1 and 2. Loss-of-function mutations of hpo rescued Caz knockdown-induced eye- and neuron-specific defects. The decreased Caz levels in nuclei induced by Caz knockdown were also rescued by loss of function mutations of hpo. Moreover, hpo mRNA level was dramatically increased in Caz knockdown larvae, indicating that Caz negatively regulated hpo. Our results demonstrate that hpo, Drosophila MST, is a novel modifier of Drosophila FUS. Therapeutic targets that inhibit the function of MST could modify the pathogenic processes of ALS. |
| 巻・号 | 371(2) |
| ページ | 311-321 |
| 公開日 | 2018-10-15 |
| DOI | 10.1016/j.yexcr.2018.08.001 |
| PII | S0014-4827(18)30636-0 |
| PMID | 30092221 |
| MeSH | Amyotrophic Lateral Sclerosis / genetics Amyotrophic Lateral Sclerosis / metabolism Amyotrophic Lateral Sclerosis / pathology Animals Cell Cycle Proteins / genetics* Cell Cycle Proteins / metabolism Cytoskeletal Proteins / genetics* Cytoskeletal Proteins / metabolism Disease Models, Animal Drosophila Proteins / deficiency Drosophila Proteins / genetics* Drosophila Proteins / metabolism Drosophila melanogaster / cytology Drosophila melanogaster / genetics* Drosophila melanogaster / growth & development Drosophila melanogaster / metabolism Eye / metabolism Eye / ultrastructure Gene Expression Regulation, Developmental Gene Knockdown Techniques Humans Intracellular Signaling Peptides and Proteins / genetics* Intracellular Signaling Peptides and Proteins / metabolism Larva / cytology Larva / genetics* Larva / growth & development Larva / metabolism Motor Neurons / metabolism Motor Neurons / pathology Nerve Degeneration Neurogenesis / genetics* Presynaptic Terminals / metabolism Presynaptic Terminals / ultrastructure Protein Serine-Threonine Kinases / genetics* Protein Serine-Threonine Kinases / metabolism RNA, Messenger / genetics RNA, Messenger / metabolism RNA-Binding Proteins / genetics* Signal Transduction Transcription Factor TFIID / deficiency Transcription Factor TFIID / genetics* |
| IF | 3.329 |
| 引用数 | 4 |
| リソース情報 | |
| ショウジョウバエ | |