| Budget Amount *help |
¥113,230,000 (Direct Cost: ¥87,100,000、Indirect Cost: ¥26,130,000)
Fiscal Year 2015: ¥20,410,000 (Direct Cost: ¥15,700,000、Indirect Cost: ¥4,710,000)
Fiscal Year 2014: ¥20,410,000 (Direct Cost: ¥15,700,000、Indirect Cost: ¥4,710,000)
Fiscal Year 2013: ¥21,450,000 (Direct Cost: ¥16,500,000、Indirect Cost: ¥4,950,000)
Fiscal Year 2012: ¥21,320,000 (Direct Cost: ¥16,400,000、Indirect Cost: ¥4,920,000)
Fiscal Year 2011: ¥29,640,000 (Direct Cost: ¥22,800,000、Indirect Cost: ¥6,840,000)
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| Outline of Final Research Achievements |
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. We showed that the ablation of TLS dysregulates the subcellular location and functions of Mena. When TLS knockout 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, Mena’s ability to suppress the motility of cells was lost in TLS knockout MEFs. Moreover, Mena failed to promote neurite outgrowth in TLS knockout primary neurons. Taken together, TLS is intimately involved in the local cytoskeletal dynamics surrounding Mena in both fibroblasts and neurons.
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