Unconventional secretion of tissue transglutaminase involves phospholipid-dependent delivery into recycling endosomes.
Unconventional secretion of tissue transglutaminase involves phospholipid-dependent delivery into recycling endosomes.
复制标题
DOI：
10.1371/journal.pone.0019414
复制
发表时间：
2011-04-27
期刊：
影响因子：
3.7
通讯作者：
Belkin AM
中科院分区：
文献类型：
--
作者：
Zemskov EA;Mikhailenko I;Hsia RC;Zaritskaya L;Belkin AM
虽然内体室室被认为在非常规蛋白质分泌中起作用，但很少有实验证据表明这种参与。在这里，我们报告循环内体是必不可少的细胞质分泌蛋白组织转谷氨酰胺酶（tTG）的外化。重新合成的细胞质tTG不遵循经典的内质网/高尔基依赖性分泌途径，而是靶向核周循环内体，并在外化之前在这些囊泡内传递。在其到达细胞表面的途径中，tTG与循环内体内内化的β1整合素相互作用，并与循环β1整合素复合物分泌。再循环核内体失活，阻止核内体与质膜融合，或下调控制核周围再循环核内体向外运输的Rab11 GTPase，都可以消除tTG的分泌。胞质tTG的初始募集以循环内体和随后的外化依赖于其与内体膜上的磷酸肌苷的结合。这些发现开始揭示tTG分泌的非常规机制，即利用内体循环途径的长环，并表明内体运输参与非经典蛋白分泌。
Although endosomal compartments have been suggested to play a role in unconventional protein secretion, there is scarce experimental evidence for such involvement. Here we report that recycling endosomes are essential for externalization of cytoplasmic secretory protein tissue transglutaminase (tTG). The de novo synthesized cytoplasmic tTG does not follow the classical ER/Golgi-dependent secretion pathway, but is targeted to perinuclear recycling endosomes, and is delivered inside these vesicles prior to externalization. On its route to the cell surface tTG interacts with internalized β1 integrins inside the recycling endosomes and is secreted as a complex with recycled β1 integrins. Inactivation of recycling endosomes, blocking endosome fusion with the plasma membrane, or downregulation of Rab11 GTPase that controls outbound trafficking of perinuclear recycling endosomes, all abrogate tTG secretion. The initial recruitment of cytoplasmic tTG to recycling endosomes and subsequent externalization depend on its binding to phosphoinositides on endosomal membranes. These findings begin to unravel the unconventional mechanism of tTG secretion which utilizes the long loop of endosomal recycling pathway and indicate involvement of endosomal trafficking in non-classical protein secretion.
登录
查看更多内容
影响因子：
11.8
作者：
Macia, Eric;Ehrlich, Marcelo;Kirchhausen, Tomas
通讯作者：
Kirchhausen, Tomas
影响因子：
4.8
作者：
Akimov, SS;Belkin, AM
通讯作者：
Belkin, AM
影响因子：
20.3
作者：
Akimov, SS;Belkin, AM
通讯作者：
Belkin, AM
DOI：
10.1083/jcb.200408165
发表时间：
2004-11-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ang AL;Taguchi T;Francis S;Fölsch H;Murrells LJ;Pypaert M;Warren G;Mellman I
通讯作者：
Mellman I
影响因子：
3.3
作者：
Hobman, TC;Zhao, BP;Farquhar, MG
通讯作者：
Farquhar, MG