Distinct Roles for the N- and C-terminal Regions of M-Sec in Plasma Membrane Deformation during Tunneling Nanotube Formation.

Distinct Roles for the N- and C-terminal Regions of M-Sec in Plasma Membrane Deformation during Tunneling Nanotube Formation.
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DOI:
10.1038/srep33548
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发表时间:
2016-09-15
期刊:
影响因子:
4.6
通讯作者:
Fukai S
Fukai S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kimura S;Yamashita M;Yamakami-Kimura M;Sato Y;Yamagata A;Kobashigawa Y;Inagaki F;Amada T;Hase K;Iwanaga T;Ohno H;Fukai S

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隧道纳米管(TNT)是一种用于细胞间通讯的结构,是介导各种信号分子和细胞成分运输的薄膜突起。 M-Sec 具有强大的膜变形能力,并与 Ral/exocyst 复合物配合诱导 TNT 形成。在这里,我们发现 M-Sec 的 N 端多元区域直接结合磷脂酰肌醇 (4,5)-二磷酸,在 TNT 形成的初始阶段定位到质膜。我们进一步报道了 M-Sec 的晶体结构,它由排列成直棒状的螺旋束组成,类似于膜束缚复合物亚基。 M-Sec 与活性 RalA 相互作用以延伸质膜突起,需要 C 端结构域中带正电荷的表面。我们的结果表明,膜相关的 M-Sec 招募活性 RalA,指导外囊复合物形成 TNT。
The tunneling nanotube (TNT) is a structure used for intercellular communication, and is a thin membrane protrusion mediating transport of various signaling molecules and cellular components. M-Sec has potent membrane deformation ability and induces TNT formation in cooperation with the Ral/exocyst complex. Here, we show that the N-terminal polybasic region of M-Sec directly binds phosphatidylinositol (4,5)-bisphosphate for its localization to the plasma membrane during the initial stage of TNT formation. We further report a crystal structure of M-Sec, which consists of helix bundles arranged in a straight rod-like shape, similar to the membrane tethering complex subunits. A positively charged surface in the C-terminal domains is required for M-Sec interaction with active RalA to extend the plasma membrane protrusions. Our results suggest that the membrane-associated M-Sec recruits active RalA, which directs the exocyst complex to form TNTs.
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