2016年4月
Translocated in liposarcoma regulates the distribution and function of mammalian enabled, a modulator of actin dynamics
FEBS JOURNAL
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- 巻
- 283
- 号
- 8
- 開始ページ
- 1475
- 終了ページ
- 1487
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1111/febs.13685
- 出版者・発行元
- WILEY
Translocated in liposarcoma/fused in sarcoma (TLS/FUS) is an RNA-binding protein that regulates the splicing pattern of mRNA transcripts and is known to cause a type of familial amyotrophic lateral sclerosis (ALS). In the absence of TLS, Mammalian enabled (Mena), an actin-regulatory protein and a target of TLS, undergoes preferential alternative splicing. In the present study, we show that the ablation of TLS dysregulates the subcellular location and functions of Mena. When TLS knockout (KO) mouse embryonic fibroblasts (MEFs) were transfected with wild-type Mena, it no longer accumulated at focal adhesions and peripheral structures, whereas the localization of the alternatively spliced form was maintained. Additionally, the ability of Mena to suppress the motility of cells was lost in TLS KO MEFs. Moreover, Mena failed to promote neurite outgrowth in TLS KO primary neurons. Taken together, TLS is intimately involved in the local cytoskeletal dynamics surrounding Mena in both fibroblasts and neurons. The robust change in cytoskeletal dynamics, as indicated by the dysregulation of Mena in TLS KO cells, provides a new insight into the pathogenesis of certain types of ALS.
- リンク情報
- ID情報
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- DOI : 10.1111/febs.13685
- ISSN : 1742-464X
- eISSN : 1742-4658
- PubMed ID : 26896672
- Web of Science ID : WOS:000374680500009