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論文
タイトル
タイトル(英)
Lemur tail kinase 1 (LMTK1) regulates the endosomal localization of β-secretase BACE1.
参照URL
https://researchmap.jp/masatohasegawa/published_papers/35097426
著者
著者(英)
Keisuke Komaki,Tetsuya Takano,Yutaka Sato,Akiko Asada,Shikito Ikeda,Kaoru Yamada,Ran Wei,Anni Huo,Aoi Fukuchi,Taro Saito,Kanae Ando,Shigeo Murayama,Wataru Araki,Fuyuki Kametani,Masato Hasegawa,Takeshi Iwatsubo,Mineko Tomomura,Mitsunori Fukuda,Shin-Ichi Hisanaga
概要
概要(英)
Lemur tail kinase 1 (LMTK1), previously called apoptosis-associated tyrosine kinase (AATYK), is an endosomal Ser/Thr kinase. We recently reported that LMTK1 regulates axon outgrowth, dendrite arborization and spine formation via Rab11-mediated vesicle transport. Rab11, a small GTPase regulating recycling endosome trafficking, is shown to be associated with late-onset Alzheimer's disease (LOAD). In fact, genome-wide association studies identified many proteins regulating vesicle transport as risk factors for LOAD. Furthermore, LMTK1 has been reported to be a risk factor for frontotemporal dementia. Then, we hypothesized that LMTK1 contributes to AD development through vesicle transport and examined the effect of LMTK1 on the cellular localization of AD-related proteins, amyloid precursor protein (APP) and β-site APP cleaving enzyme 1 (BACE1). The β-cleavage of APP by BACE1 is the initial and rate-limiting step in Aβ generation. We found that LMTK1 accumulated BACE1, but not APP, to the perinuclear endosomal compartment, whereas the kinase-negative (kn) mutant of LMTK1A did not. The β-C-terminal fragment was prone to increase under overexpression of LMTK1A kn. Moreover, the expression level of LMTK1A was reduced in AD brains. These results suggest the possibility that LMTK1 is involved in AD development through the regulation of the proper endosomal localization of BACE1.
出版者・発行元
出版者・発行元(英)
誌名
誌名(英)
Journal of biochemistry
開始ページ
終了ページ
出版年月
2021年9月15日
査読の有無
招待の有無
掲載種別
研究論文(学術雑誌)
ISSN
DOI URL
https://doi.org/10.1093/jb/mvab094
共同研究・競争的資金等の研究課題
研究者
亀谷 富由樹 (カメタニ フユキ) , Hasegawa Masato