Interaction of TBC1D9B with Mammalian ATG8 Homologues Regulates Autophagic Flux.
Interaction of TBC1D9B with Mammalian ATG8 Homologues Regulates Autophagic Flux.
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DOI：
10.1038/s41598-018-32003-2
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发表时间：
2018-09-10
影响因子：
4.6
通讯作者：
Yin XM
中科院分区：
文献类型：
--
作者：
Liao Y;Li M;Chen X;Jiang Y;Yin XM
自噬体是具有胞质组分的双膜囊泡。它们的目的地是与溶酶体融合，降解包裹的货物。然而，自噬体可能与其他膜隔室融合，并可能被来自这些隔室的RAB分子误导。人们对确保适当贩运的机制了解不多。酵母ATG8及其哺乳动物同源物在自噬体的形成和扩增中起关键作用。我们推测它们也可能参与自噬体运输的调节。利用酵母双杂交系统，我们发现TBC1D9B，一个GT3激活蛋白的RAB11A，与LC3B相互作用。TBC1D9B还可以与其他哺乳动物ATG8同源物相互作用。这种相互作用被证实与纯化的蛋白质在体外，并在体内通过免疫共沉淀。进一步确定了TBC1D9B与LC 3的相互作用结构域，这是独特的，不同于先前在其他LC 3相互作用分子中定义的已知LC 3相互作用区域。在功能上，TBC1D9B可以与LC 3B共定位在自噬体膜上。TBC1D9B的抑制抑制膜结合LC 3B的周转和长寿命蛋白的自噬降解。因此，TBC1D9B可以积极调节自噬通量，可能是通过其对RAB11A的GT3活性，促进自噬体的适当目的地降解。
Autophagosomes are double-membraned vesicles with cytosolic components. Their destination is to fuse with the lysosome to degrade the enclosed cargo. However, autophagosomes may be fused with other membrane compartments and possibly misguided by the RAB molecules from these compartments. The mechanisms ensuring the proper trafficking are not well understood. Yeast ATG8 and its mammalian homologues are critically involved in the autophagosome formation and expansion. We hypothesized that they could be also involved in the regulation of autophagosome trafficking. Using the yeast two-hybrid system, we found that TBC1D9B, a GTPase activating protein for RAB11A, interacted with LC3B. TBC1D9B could also interact with other mammalian ATG8 homologues. This interaction was confirmed with purified proteins in vitro, and by co-immunoprecipitation in vivo. The interacting domain of TBC1D9B with LC3 was further determined, which is unique and different from the known LC3-interacting region previously defined in other LC3-interacting molecules. Functionally, TBC1D9B could be co-localized with LC3B on the autophagosome membranes. Inhibition of TBC1D9B suppressed the turnover of membrane-bound LC3B and the autophagic degradation of long-lived proteins. TBC1D9B can thus positively regulate autophagic flux, possibly through its GTPase activity to inactivate RAB11A, facilitating the proper destination of the autophagosomes to the degradation.
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影响因子：
64.8
作者：
Ichimura, Y;Kirisako, T;Ohsumi, Y
通讯作者：
Ohsumi, Y
影响因子：
4.8
作者：
Chen, Yun;Decker, Keith F.;Dorn, Gerald W., II
通讯作者：
Dorn, Gerald W., II
影响因子：
64.5
作者：
Nakatogawa, Hitoshi;Ichimura, Yoshinobu;Ohsumi, Yoshinori
通讯作者：
Ohsumi, Yoshinori
影响因子：
4.8
作者：
Li, Min;Khambu, Bilon;Yin, Xiao-Ming
通讯作者：
Yin, Xiao-Ming
DOI：
10.1016/j.molbrainres.2003.09.011
发表时间：
2003-11-26
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Nemos, C;Mansuy, V;Delage-Mourroux, R
通讯作者：
Delage-Mourroux, R