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Translocated in liposarcoma regulates the distribution and function of mammalian enabled, a modulator of actin dynamics
Author(s) -
Sugiura Tomohito,
Matsuda Shuji,
Kurosaka Satoshi,
Nakai Nobuhiro,
Fukumoto Keita,
Takahashi Tetsuya,
Maruyama Hirofumi,
Imaizumi Kazunori,
Matsumoto Masayasu,
Takumi Toru
Publication year - 2016
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13685
Subject(s) - microbiology and biotechnology , cytoskeleton , alternative splicing , actin , transfection , biology , rna binding protein , actin cytoskeleton , neurite , motility , messenger rna , gene , cell , genetics , in vitro
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 ( MEF s) 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 MEF s. 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 .