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Implication of deregulated vesicles' traffic in the occurence of acute leukemia

囊泡运输失调对急性白血病发生的影响

基本信息

批准号：
23501256
负责人：
SATAKE Masanobu
金额：
$ 3.33万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2011
资助国家：
日本
起止时间：
2011 至 2013
项目状态：
已结题

项目摘要

The formation of clathrin-coated vesicles is essential for intracellular membrane trafficking and is triggered by the ARF GTPases. We previously identified SMAP1 as an ARF GTPase-activating protein.We targeted Smap1 in mice and Smap1-deficent erythroblasts exhibited enhanced transferrin endocytosis. In addition, Smap1 deficiency impaired the sorting of internalized c-Kit from multivesicular bodies to lysosomes, resulting in accumulation of c-KIT that was accompanied by enhanced activation of ERK and increased cell growth. Interestingly, aged Smap1-deficient mice developed anemia associated with morphologically dysplastic cells of erythroid-myeloid lineage, which are abnormalities similar to myelodysplastic syndrome (MDS) in humans. Furthermore, some Smap1-deficient mice developed acute myeloid leukemia (AML) of various subtypes. Collectively, the deregulation of clathrin-dependent membrane trafficking is likely involved in the development of MDS and subsequent AML.

网格蛋白包被的囊泡的形成是细胞内膜运输所必需的，并且由ARF GTP酶触发。我们先前鉴定SMAP 1为ARF GTP酶激活蛋白，我们在小鼠中靶向Smap 1，Smap 1缺陷的成红细胞表现出增强的转铁蛋白内吞作用。此外，Smap 1缺陷损害了从多泡体到溶酶体的内化c-Kit的分选，导致c-KIT的积累，伴随着ERK的活化增强和细胞生长增加。有趣的是，老年Smap 1缺陷小鼠发生与红系-髓系形态发育不良细胞相关的贫血，这是与人类骨髓增生异常综合征（MDS）相似的异常。此外，一些Smap 1缺陷小鼠发展成各种亚型的急性髓性白血病（AML）。总的来说，网格蛋白依赖性膜运输的失调可能参与MDS和随后的AML的发展。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The Arf GAP SMAP2 is necessary for organized vesicle budding from the trans-Golgi network and subsequent acrosome formation in spermiogenesis.

DOI：
10.1091/mbc.e13-05-0234
发表时间：
2013-09
期刊：
Molecular biology of the cell
影响因子：
3.3
作者：
Funaki T;Kon S;Tanabe K;Natsume W;Sato S;Shimizu T;Yoshida N;Wong WF;Ogura A;Ogawa T;Inoue K;Ogonuki N;Miki H;Mochida K;Endoh K;Yomogida K;Fukumoto M;Horai R;Iwakura Y;Ito C;Toshimori K;Watanabe T;Satake M
通讯作者：
Satake M

Localization of SMAP2 to the TGN and its Function in the Regulation of TGN Protein Transport

SMAP2 对 TGN 的定位及其在 TGN 蛋白转运调节中的功能

DOI：
10.1247/csf.10022
发表时间：
2011
期刊：
Cell Structure and Function
影响因子：
1.5
作者：
Tomo Funaki;Shunsuke Kon;Roger E Ronn;Yuji Henmi;Yuka Kobayashi;Toshio Watanabe;Keiko Nakayama;Kenji Tanabe;Masanobu Satake
通讯作者：
Masanobu Satake

Putative terminator and/or effector functions of Arf GAPs in the trafficking of clathrin-coated vesicles.

Arf GAP 在网格蛋白包被囊泡运输中的假定终止子和/或效应子功能。