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研究発表を行った学会；
・第89回日本薬理学会年会
　2016年3月9日〜11日（横浜）

タイトル；Effect of mutant TMEM240 that causes spinocerebellar ataxia 21 on neural morphology.
発表者；関　貴弘　氏
　　　（熊本大学　大学院生命科学研究部　薬物活性学分野）
要旨；
Spinocerbellar ataxia 21 (SCA21) is an autosomal dominant neurodegenerative disease, characterized by an early-onset and slowly progressive ataxia. Missense and nonsense mutations of TMEM240 gene coding transmembrane protein 240 have been identified as a causal gene of SCA21. TMEM240 is predicted as a membrane protein, but its function remains unknown. We revealed that TMEM240 localizes around the large vesicles and regulates intracellular lipid accumulation and autophagy in overexpressed HeLa cells. In the present study, we examined whether TMEM240 affects primary cultured neurons. Since endogenous TMEM240 highly expresses in cerebral cortex and cerebellum, we prepared primary cultured neurons from these regions of rat embryos. We first expressed GFP and TMEM240 to cortex neurons using adeno-associated viral (AAV) vectors. Although wild-type (WT) TMEM240 significantly impaired neurite outgrowth, this impairment was reversed by SCA21 mutant TMEM240. Next, we expressed GFP and TMEM240 to cerebellar Purkinje cells (PCs). WT TMEM240 did not affect PC morphology, while SCA21 mutant TMEM240 impaired the dendritic development. These findings suggest that SCA21 mutations in TMEM240 affect neural morphology, which might be related to SCA21 pathogenesis.